Ureteral and Bladder Catheters and Methods of Inducing Negative Pressure to Increase Renal Perfusion

ABSTRACT

A ureteral catheter includes a drainage lumen including a proximal portion configured to be positioned in at least a portion of a patient&#39;s urethra and/or bladder and a distal portion configured to be positioned in a patient&#39;s kidney, renal pelvis, and/or in the ureter adjacent to the renal pelvis, the distal portion including a retention portion for maintaining positioning of the distal portion of the drainage lumen, the retention portion including two or more openings on a sidewall of the retention portion for permitting fluid flow into the drainage lumen, wherein a number of the openings nearer to a distal end of the retention portion is greater than a number of the opening(s) nearer to a proximal end of the retention portion.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/817,773, filed Mar. 13, 2020, which is a divisional of U.S. patentapplication Ser. No. 15/687,083 filed Aug. 25, 2017, now issued as U.S.Pat. No. 10,926,062, which is a continuation-in-part of U.S. patentapplication Ser. No. 15/411,884 filed Jan. 20, 2017, now issued as U.S.Pat. No. 10,512,713, which is a continuation-in-part of U.S. patentapplication Ser. No. 15/214,955 filed Jul. 20, 2016, now issued as U.S.Pat. No. 10,307,564, which claims the benefit of U.S. ProvisionalApplication No. 62/300,025 filed Feb. 25, 2016, U.S. ProvisionalApplication No. 62/278,721, filed Jan. 14, 2016, U.S. ProvisionalApplication No. 62/260,966 filed Nov. 30, 2015, and U.S. ProvisionalApplication No. 62/194,585, filed Jul. 20, 2015, each of which isincorporated herein by reference in its entirety.

BACKGROUND Technical Field

The present disclosure relates to methods and devices for treatingimpaired renal function across a variety of disease states and, inparticular, to catheter devices, assemblies, and methods for collectionof urine and/or inducement of negative pressure in the ureters and/orkidneys.

Background

The renal or urinary system includes a pair of kidneys, each kidneybeing connected by a ureter to the bladder, and a urethra for drainingurine produced by the kidneys from the bladder. The kidneys performseveral vital functions for the human body including, for example,filtering the blood to eliminate waste in the form of urine. The kidneysalso regulate electrolytes (e.g., sodium, potassium and calcium) andmetabolites, blood volume, blood pressure, blood pH, fluid volume,production of red blood cells, and bone metabolism. Adequateunderstanding of the anatomy and physiology of the kidneys is useful forunderstanding the impact that altered hemodynamics other fluid overloadconditions have on their function.

In normal anatomy, the two kidneys are located retroperitoneally in theabdominal cavity. The kidneys are bean-shaped encapsulated organs. Urineis formed by nephrons, the functional unit of the kidney, and then flowsthrough a system of converging tubules called collecting ducts. Thecollecting ducts join together to form minor calyces, then majorcalyces, which ultimately join near the concave portion of the kidney(renal pelvis). A major function of the renal pelvis is to direct urineflow to the ureter. Urine flows from the renal pelvis into the ureter, atube-like structure that carries the urine from the kidneys into thebladder. The outer layer of the kidney is called the cortex, and is arigid fibrous encapsulation. The interior of the kidney is called themedulla. The medulla structures are arranged in pyramids.

Each kidney is made up of approximately one million nephrons. Aschematic drawing of a nephron 1102 is shown in FIG. 39. Each nephronincludes the glomerulus 1110, Bowman's capsule 1112, and tubules 1114.The tubules 1114 include the proximal convoluted tubule 1116, the loopof Henle 1118, the distal convoluted tubule 1120, and the collectingduct 1122. The nephrons 1102 contained in the cortex layer of the kidneyare distinct from the anatomy of those contained in the medulla. Theprincipal difference is the length of the loop of Henle 1118. Medullarynephrons contain a longer loop of Henle, which, under normalcircumstances, allows greater regulation of water and sodiumreabsorption than in the cortex nephrons.

The glomerulus is the beginning of the nephron, and is responsible forthe initial filtration of blood. Afferent arterioles pass blood into theglomerular capillaries, where hydrostatic pressure pushes water andsolutes into Bowman's capsule. Net filtration pressure is expressed asthe hydrostatic pressure in the afferent arteriole minus the hydrostaticpressure in Bowman's space minus the osmotic pressure in the efferentarteriole.

Net Filtration Pressure=Hydrostatic Pressure(AfferentArteriole)−Hydrostatic Pressure(Bowman's Space)−OsmoticPressure(Efferent Arteriole)  (Equation 1)

The magnitude of this net filtration pressure defined by Equation 1determines how much ultra-filtrate is formed in Bowman's space anddelivered to the tubules. The remaining blood exits the glomerulus viathe efferent arteriole. Normal glomerular filtration, or delivery ofultra-filtrate into the tubules, is about 90 ml/min/1.73 m².

The glomerulus has a three-layer filtration structure, which includesthe vascular endothelium, a glomerular basement membrane, and podocytes.Normally, large proteins such as albumin and red blood cells, are notfiltered into Bowman's space. However, elevated glomerular pressures andmesangial expansion create surface area changes on the basement membraneand larger fenestrations between the podocytes allowing larger proteinsto pass into Bowman's space.

Ultra-filtrate collected in Bowman's space is delivered first to theproximal convoluted tubule. Re-absorption and secretion of water andsolutes in the tubules is performed by a mix of active transportchannels and passive pressure gradients. The proximal convoluted tubulesnormally reabsorb a majority of the sodium chloride and water, andnearly all glucose and amino acids that were filtered by the glomerulus.The loop of Henle has two components that are designed to concentratewastes in the urine. The descending limb is highly water permeable andreabsorbs most of the remaining water. The ascending limb reabsorbs 25%of the remaining sodium chloride, creating a concentrated urine, forexample, in terms of urea and creatinine. The distal convoluted tubulenormally reabsorbs a small proportion of sodium chloride, and theosmotic gradient creates conditions for the water to follow.

Under normal conditions, there is a net filtration of approximately 14mmHg. The impact of venous congestion can be a significant decrease innet filtration, down to approximately 4 mmHg. See Jessup M., Thecardiorenal syndrome: Do we need a change of strategy or a change oftactics?, JACC 53(7):597-600, 2009 (hereinafter “Jessup”). The secondfiltration stage occurs at the proximal tubules. Most of the secretionand absorption from urine occurs in tubules in the medullary nephrons.Active transport of sodium from the tubule into the interstitial spaceinitiates this process. However, the hydrostatic forces dominate the netexchange of solutes and water. Under normal circumstances, it isbelieved that 75% of the sodium is reabsorbed back into lymphatic orvenous circulation. However, because the kidney is encapsulated, it issensitive to changes in hydrostatic pressures from both venous andlymphatic congestion. During venous congestion the retention of sodiumand water can exceed 85%, further perpetuating the renal congestion. SeeVerbrugge et al., The kidney in congestive heart failure: Arenatriuresis, sodium, and diruetucs really the good, the bad and theugly? European Journal of Heart Failure 2014:16, 133-42 (hereinafter“Verbrugge”).

Venous congestion can lead to a prerenal form of acute kidney injury(AKI). Prerenal AKI is due to a loss of perfusion (or loss of bloodflow) through the kidney. Many clinicians focus on the lack of flow intothe kidney due to shock. However, there is also evidence that a lack ofblood flow out of the organ due to venous congestion can be a clinicallyimportant sustaining injury. See Damman K, Importance of venouscongestion for worsening renal function in advanced decompensated heartfailure, JACC 17:589-96, 2009 (hereinafter “Damman”).

Prerenal AKI occurs across a wide variety of diagnoses requiringcritical care admissions. The most prominent admissions are for sepsisand Acute Decompensated Heart Failure (ADHF). Additional admissionsinclude cardiovascular surgery, general surgery, cirrhosis, trauma,burns, and pancreatitis. While there is wide clinical variability in thepresentation of these disease states, a common denominator is anelevated central venous pressure. In the case of ADHF, the elevatedcentral venous pressure caused by heart failure leads to pulmonaryedema, and, subsequently, dyspnea in turn precipitating the admission.In the case of sepsis, the elevated central venous pressure is largely aresult of aggressive fluid resuscitation. Whether the primary insult waslow perfusion due to hypovolemia or sodium and fluid retention, thesustaining injury is the venous congestion resulting in inadequateperfusion.

Hypertension is another widely recognized state that createsperturbations within the active and passive transport systems of thekidney(s). Hypertension directly impacts afferent arteriole pressure andresults in a proportional increase in net filtration pressure within theglomerulus. The increased filtration fraction also elevates theperitubular capillary pressure, which stimulates sodium and waterre-absorption. See Verbrugge.

Because the kidney is an encapsulated organ, it is sensitive to pressurechanges in the medullary pyramids. The elevated renal venous pressurecreates congestion that leads to a rise in the interstitial pressures.The elevated interstitial pressures exert forces upon both theglomerulus and tubules. See Verburgge. In the glomerulus, the elevatedinterstitial pressures directly oppose filtration. The increasedpressures increase the interstitial fluid, thereby increasing thehydrostatic pressures in the interstitial fluid and peritubularcapillaries in the medulla of the kidney. In both instances, hypoxia canensue leading to cellular injury and further loss of perfusion. The netresult is a further exacerbation of the sodium and water re-absorptioncreating a negative feedback. See Verbrugge, 133-42. Fluid overload,particularly in the abdominal cavity is associated with many diseasesand conditions, including elevated intra-abdominal pressure, abdominalcompartment syndrome, and acute renal failure. Fluid overload can beaddressed through renal replacement therapy. See Peters, C. D., Shortand Long-Term Effects of the Angiotensin II Receptor BlockerIrbesartanon Intradialytic Central Hemodynamics: A RandomizedDouble-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIRStudy), PLoS ONE (2015) 10(6): e0126882.doi:10.1371/journal.pone.0126882 (hereinafter “Peters”). However, such aclinical strategy provides no improvement in renal function for patientswith the cardiorenal syndrome. See Bart B, Ultrafiltration indecompensated heart failure with cardiorenal syndrome, NEJM 2012;367:2296-2304 (hereinafter “Bart”).

In view of such problematic effects of fluid retention, devices andmethods for improving removal of urine from the urinary tract and,specifically for increasing quantity and quality of urine output fromthe kidneys, are needed.

SUMMARY

According to one example, a ureteral catheter includes a drainage lumenhaving a proximal portion configured to be positioned in at least aportion of a patient's urethra and/or bladder and a distal portionconfigured to be positioned in a patient's kidney, renal pelvis, and/orin the ureter adjacent to the renal pelvis. The distal portion includesa retention portion for maintaining positioning of the distal portion ofthe drainage lumen. The retention portion includes a plurality ofsections, each section having one or more openings on a sidewall of theretention portion for permitting fluid flow into the drainage lumen. Atotal area of openings of a first section of the plurality of sectionsis less than a total area of openings of an adjacent second section ofthe plurality of sections. The second section is closer to a distal endof the drainage lumen than the first section.

According to another example, a ureteral catheter includes a drainagelumen having a proximal portion configured to be positioned in at leasta portion of a patient's urethra and a distal portion configured to bepositioned in a patient's kidney, renal pelvis, and/or in the ureteradjacent to the renal pelvis. The distal portion includes a retentionportion for maintaining positioning of the distal portion of thedrainage lumen. The retention portion includes a plurality of equallength sections of the drainage lumen, each of which has one or moreopenings on a sidewall of the drainage lumen for permitting fluid flowinto the drainage lumen. A volumetric flow rate for fluid flowing into aproximal-most section of the plurality of sections is between about 1%and 60%, preferably between about 10% and 60%, and more preferablybetween about 30% and 60%, of a volumetric flow rate of fluid flowingthrough the proximal portion of the drainage lumen, as calculated basedon a mass transfer shell balance evaluation for calculating volumetricflow rates through openings of the sections when a negative pressure of−45 mmHg is applied to a proximal end of the drainage lumens.

According to another example, a ureteral catheter includes: a drainagelumen having a proximal portion configured to be positioned in at leasta portion of a patient's urethra and/or bladder and a distal portionconfigured to be positioned in a patient's kidney, renal pelvis, and/orin the ureter adjacent to the renal pelvis. The distal portion includesa coiled retention portion for maintaining positioning of the distalportion of the drainage lumen. The coiled retention portion includes: atleast a first coil having a first diameter extending about an axis ofthe retention portion that is at least partially coextensive with astraight or curvilinear central axis of a portion of the drainage lumenproximal to the retention portion; and a plurality of sections, each ofwhich includes one or more openings on a sidewall of the retentionportion for permitting fluid flow into the drainage lumen. Along theplurality of sections, the sidewall of the retention portion includes aradially inwardly facing side and a radially outwardly facing side. Atotal area of the openings on the radially inwardly facing side isgreater than a total area of the openings on the radially outwardlyfacing side. A total area of openings of a first section of theplurality of sections is less than a total area of openings of anadjacent second section of the plurality of sections, when the secondsection is closer to a distal end of the drainage lumen than the firstsection.

According to another example, a ureteral catheter includes a drainagelumen having a proximal portion configured to be positioned in at leasta portion of a patient's urethra and/or bladder and a distal portionconfigured to be positioned in a patient's kidney, renal pelvis, and/orin the ureter adjacent to the renal pelvis. The distal portion includesa retention portion for maintaining positioning of the distal portion ofthe drainage lumen. The retention portion includes a plurality ofopenings on a sidewall of the retention portion for permitting fluidflow into the drainage lumen. An area of an opening of the plurality ofopenings which is closer to a proximal end of the retention portion isless than an area of an opening of the plurality of openings which iscloser to the distal end of the drainage lumen.

According to another example, a system for inducing negative pressure ina portion of a urinary tract of a patient includes at least one ureteralcatheter including a drainage lumen having a proximal portion configuredto be positioned in at least a portion of a patient's urethra and/orbladder and a distal portion configured to be positioned in a patient'skidney, renal pelvis, and/or in the ureter adjacent to the renal pelvis.The distal portion includes a retention portion for maintainingpositioning of the distal portion of the drainage lumen. The retentionportion includes a plurality of equal length sections of the drainagelumen, each of which includes one or more openings on a sidewall of thedrainage lumen for permitting fluid flow into the drainage lumen. Thesystem also includes a pump in fluid communication with the drainagelumen of the at least one ureteral catheter. The pump is configured forinducing a positive and/or a negative pressure in a portion of theurinary tract of the patient to draw fluid into the drainage lumenthrough the openings of the sections of the retention portion. A totalarea of openings of a first section of the plurality of sections is lessthan a total area of openings of an adjacent second section of theplurality of sections, when the second section is closer to a distal endof the drainage lumen than the first section.

Non-limiting examples, aspects or embodiments of the present inventionwill now be described in the following numbered clauses:

Clause 1: A ureteral catheter, comprising: a drainage lumen comprising aproximal portion configured to be positioned in at least a portion of apatient's urethra and/or bladder and a distal portion configured to bepositioned in a patient's kidney, renal pelvis, and/or in the ureteradjacent to the renal pelvis, the distal portion comprising a retentionportion for maintaining positioning of the distal portion of thedrainage lumen, the retention portion comprising a plurality ofsections, each section comprising one or more openings on a sidewall ofthe retention portion for permitting fluid flow into the drainage lumen,wherein a total area of openings of a first section of the plurality ofsections is less than a total area of openings of an adjacent secondsection of the plurality of sections, the second section being closer toa distal end of the drainage lumen than the first section.

Clause 2: The ureteral catheter of clause 1, wherein the proximalportion of the drainage lumen is essentially free of or free ofopenings.

Clause 3: The ureteral catheter of clause 1 or clause 2, wherein theproximal portion of the drainage lumen is configured to extend outsideof the patient's body.

Clause 4: The ureteral catheter of any of clauses 1 to 3, furthercomprising a plurality of distance markings on the sidewall of theproximal portion of the drainage lumen to indicate how far the catheteris inserted into a urinary tract of a body of the patient.

Clause 5: The ureteral catheter of clause 4, further comprising aradiopaque band on the sidewall of the drainage lumen which is adjacentto a proximal end of the retention portion for identifying a location ofthe retention portion using fluoroscopic imaging, the radiopaque bandhaving a different appearance than the distance markings when viewed byfluoroscopic imaging.

Clause 6: The ureteral catheter of any of clauses 1 to 5, wherein thedrainage lumen is formed, at least in part, from one or more of copper,silver, gold, nickel-titanium alloy, stainless steel, titanium,polyurethane, polyvinyl chloride, polytetrafluoroethylene (PTFE), latex,and silicone.

Clause 7: The ureteral catheter of any of clauses 1 to 6, wherein theplurality of sections of the retention portion is biased in a coiledconfiguration, such that the retention portion comprises: at least afirst coil having a first diameter; and at least a second coil having asecond diameter, the first diameter being less than the second diameter,the second coil being closer to the distal end of the drainage lumenthan the first coil, and wherein, prior to insertion into a patient'surinary tract, a portion of the drainage lumen that is proximal to theretention portion defines a straight or curvilinear central axis, andwherein, when deployed, the first coil and the second coil of theretention portion extend about an axis of the retention portion that isat least partially coextensive with the straight or curvilinear centralaxis of the portion of the drainage lumen.

Clause 8: The ureteral catheter of clause 7, wherein a gap between thesidewall of the drainage lumen of the first coil and an adjacentsidewall of the drainage lumen of the second coil is less than 3.0 mm,preferably between about 0.25 mm and 2.5 mm, and more preferably betweenabout 0.5 mm and 2.0 mm.

Clause 9: The ureteral catheter of clause 7 or clause 8, wherein thefirst coil is a half coil extending from 0 degrees to 180 degrees and isfree from openings, wherein the second coil is a full coil extendingfrom 180 degrees to 540 degrees, and wherein the first section of theplurality of sections extends between 180 and 360 degrees of the secondcoil and the second section extends between 360 degrees and 540 degreesof the second coil.

Clause 10: The ureteral catheter of any of clauses 7 to 9, wherein,along the plurality of sections, the sidewall of the drainage lumencomprises a radially inwardly facing side and a radially outwardlyfacing side, and wherein a total area of the openings on the radiallyinwardly facing side is greater than a total area of the openings on theradially outwardly facing side.

Clause 11: The ureteral catheter of any of clauses 7 to 10, wherein theretention portion of the drainage lumen comprises a sidewall comprisinga radially inwardly facing side and a radially outwardly facing side,and wherein one or more perforations are disposed on the radiallyinwardly facing side, and wherein the radially outwardly facing side isessentially free of perforations.

Clause 12: The ureteral catheter of any of clauses 7 to 11, wherein adistal-most portion of the retention portion is bent inwardly relativeto a curvature of a distal-most coil, such that a central axis of thedistal-most portion extends from the distal end of the drainage lumentoward the axis of the retention portion.

Clause 13: The ureteral catheter of any of clauses 7 to 12, wherein thefirst diameter of the first coil is about 8 mm to 10 mm and the seconddiameter of the second coil is about 16 mm to 20 mm.

Clause 14: The ureteral catheter of any of clauses 7 to 13, wherein theretention portion further comprises a third coil extending about theaxis of the retention portion, the third coil having a diameter greaterthan or equal to either the first diameter or the second diameter, thethird coil being closer to an end of the distal portion of the drainagelumen than the second coil.

Clause 15: The ureteral catheter of any of clauses 7 to 14, wherein thedrainage lumen is transitionable between an uncoiled configuration forinsertion from the patient's bladder into the patient's ureter and thecoiled configuration for deployment within the patient's kidney, renalpelvis, and/or in the ureter adjacent to the renal pelvis.

Clause 16: The ureteral catheter of clause 15, wherein the drainagelumen is naturally biased to the coiled configuration.

Clause 17: The ureteral catheter of any of clauses 1 to 16, wherein thesections are of equal length.

Clause 18: The ureteral catheter of any of clauses 1 to 17, wherein avolumetric flow rate for fluid which flows into a second section is atleast 30% of a volumetric flow rate of fluid which flows into theopenings of the first section, as calculated based on a mass transfershell balance evaluation for calculating volumetric flow rates throughopenings of the sections when a negative pressure of −45 mmHg is appliedto a proximal end of the drainage lumen.

Clause 19: The ureteral catheter of any of clauses 1 to 18, wherein avolumetric flow rate for fluid flowing into a proximal-most section ofthe plurality of sections is less than 60% of a volumetric flow rate forfluid flowing through the proximal portion of the drainage lumen, ascalculated based on a mass transfer shell balance evaluation forcalculating volumetric flow rates through openings of the sections whena negative pressure of −45 mmHg is applied to a proximal end of thedrainage lumen.

Clause 20: The ureteral catheter of any of clauses 1 to 19, wherein avolumetric flow rate for fluid flowing into two proximal-most sectionsof the plurality of sections is less than 90% of a volumetric flow rateof fluid flowing through the proximal portion of the draining lumen, ascalculated based on a mass transfer shell balance evaluation forcalculating volumetric flow rates through openings of the sections whena negative pressure of −45 mmHg measured at an outflow port of a vacuumpump is applied to a proximal end of the drainage lumen.

Clause 21: The ureteral catheter of any of clauses 1 to 20, whereinopenings of a third section of the plurality of sections have a totalarea that is greater than the total area of the openings of the firstsection or the second section, and wherein the third section is closerto the distal end of the drainage lumen than the first section or thesecond section.

Clause 22: The ureteral catheter of any of clauses 1 to 21, wherein atotal area of the one or more openings of a section increases forsections closer to a distal end of the retention portion.

Clause 23: The ureteral catheter of any of clauses 1 to 22, wherein thedrainage lumen has an inner diameter of between about 0.5 mm and 1.5 mm,and wherein a total area of openings of the first section and/or a totalarea of openings of the second section is between about 0.002 mm² andabout 2.5 mm².

Clause 24: The ureteral catheter of any of clauses 1 to 23, wherein thedrainage lumen has an inner diameter of between about 0.5 mm and 1.5 mm,and wherein a total area of openings of the first section is betweenabout 0.002 mm² and about 1.0 mm² and a total area of openings of thesecond section is greater than about 0.5 mm².

Clause 25: The ureteral catheter of clause 24, wherein each of thesections of the plurality of sections is an equal length of betweenabout 5 mm and about 35 mm, and preferably between about 5 mm and 15 mm.

Clause 26: The ureteral catheter of any of clauses 1 to 25, wherein thedrainage lumen has an uncoiled longitudinal length of between about 30cm and about 120 cm.

Clause 27: The ureteral catheter of any of clauses 1 to 26, wherein oneor more of the openings have a cross-sectional area of between about0.002 mm² and about 0.25 mm², and wherein the second section comprisesmore openings than the first section.

Clause 28: The ureteral catheter of any of clauses 1 to 27, wherein thedrainage lumen comprises an open distal end having an inner diameter ofbetween about 0.5 mm and about 1.5 mm.

Clause 29: The ureteral catheter of any of clauses 1 to 28, wherein theopenings are circles with a diameter of between about 0.5 mm and about1.5 mm, and wherein a diameter of an opening of one of the sections isat least 0.05 mm greater than a diameter of an opening of a proximallyadjacent section.

Clause 30: The ureteral catheter of any of clauses 1 to 29, wherein adistance between a center of an opening of one of the sections and acenter of an opening of an adjacent section is between about 5.0 mm andabout 15.0 mm.

Clause 31: The ureteral catheter of any of clauses 1 to 30, wherein theopenings of the plurality of sections are circular and have a diameterof between about 0.05 mm and about 1.0 mm.

Clause 32: The ureteral catheter of any of clauses 1 to 31, wherein eachsection comprises a single opening.

Clause 33: The ureteral catheter of clause 32, wherein an area of asingle opening of a section closer to the proximal portion of thedrainage lumen is less than an area of a single opening of a sectioncloser to the distal end of the drainage lumen.

Clause 34: The ureteral catheter of clause 32 or clause 33, wherein anarea of each of the single openings is less than an area of a distallyadjacent single opening.

Clause 35: The ureteral catheter of any of clauses 32 to 34, wherein thedistal end of the drainage lumen has an opening having an area greaterthan an area of the single opening of an adjacent section of theplurality of sections.

Clause 36: The ureteral catheter of any of clauses 1 to 35, wherein eachof the openings of the plurality of sections has the same area, andwherein the second section comprises more openings than the firstsection.

Clause 37: The ureteral catheter of any of clauses 1 to 36, wherein atleast two openings of a section of the plurality of sections arearranged such that a virtual line extending around a circumference ofthe sidewall of the drainage lumen contacts at least a portion of eachof the at least two openings.

Clause 38: The ureteral catheter of any of clauses 1 to 37, wherein theopenings of at least one of the sections are arranged such that avirtual line extending along the sidewall of the drainage lumen in acurvilinear direction contacts at least a portion of each of theopenings of the respective section.

Clause 39: The ureteral catheter of any of clauses 1 to 38, whereinopenings of the first section are arranged along a first virtual lineextending in an curvilinear direction along the sidewall of the drainagelumen, wherein at least one of the openings of the second section isarranged along a second virtual line extending in a curvilineardirection along the sidewall of the drainage lumen, and wherein at leastone of the openings of the second section is arranged along a thirdvirtual line extending in a curvilinear direction along the sidewall ofthe drainage lumen.

Clause 40: The ureteral catheter of clause 39, wherein the first virtualline is not coextensive with the second virtual line and/or with thethird virtual line.

Clause 41: The ureteral catheter of clause 39 or clause 40, wherein thesecond virtual line is not coextensive with the third virtual line.

Clause 42: The ureteral catheter of any of clauses 39 to 41, wherein thefirst, second, and third virtual lines are parallel.

Clause 43: The ureteral catheter of any of clauses 1 to 42, wherein eachopening of a plurality of openings is independently selected from one ormore of circles, triangles, rectangles, ellipses, ovals, and squares.

Clause 44: A ureteral catheter, comprising: a drainage lumen comprisinga proximal portion configured to be positioned in at least a portion ofa patient's urethra and a distal portion configured to be positioned ina patient's kidney, renal pelvis, and/or in the ureter adjacent to therenal pelvis, the distal portion comprising a retention portion formaintaining positioning of the distal portion of the drainage lumen, theretention portion comprising a plurality of equal length sections of thedrainage lumen, each of which comprises one or more openings on asidewall of the drainage lumen for permitting fluid flow into thedrainage lumen, wherein a volumetric flow rate for fluid flowing into aproximal-most section of the plurality of sections is between about 1%and 60%, preferably between about 10% and 60%, and more preferablybetween about 30% and 60%, of a volumetric flow rate of fluid flowingthrough the proximal portion of the drainage lumen, as calculated basedon a mass transfer shell balance evaluation for calculating volumetricflow rates through openings of the sections when a negative pressure of−45 mmHg is applied to a proximal end of the drainage lumens.

Clause 45: The ureteral catheter of clause 44, wherein a volumetric flowrate of fluid flowing into two proximal-most sections of the pluralityof sections is between about 1% and 90%, preferably between about 30%and 90%, and more preferably between about 60% and 90% of the volumetricflow rate of fluid flowing through the proximal portion of the drainagelumen, as calculated based on a mass transfer shell balance evaluationfor calculating volumetric flow rates through openings of the sectionswhen a negative pressure of −45 mmHg is applied to a proximal end of thedrainage lumen.

Clause 46: The ureteral catheter of clause 44 or clause 45, wherein eachsection comprises a single opening, and wherein a single opening of asection closer to the proximal end of the drainage lumen is less than anarea of a single opening in a section closer to a distal end of thedrainage lumen.

Clause 47: The ureteral catheter of any of clauses 44 to 46, wherein adistal end of the drainage lumen has an opening having an area greaterthan an area of a single opening of an adjacent section of the pluralityof sections.

Clause 48: The ureteral catheter of any of clauses 44 to 47, whereineach of the openings of the plurality of sections has the same area, andwherein a second section of the plurality of sections comprises moreopenings than the proximal-most section.

Clause 49: The ureteral catheter of any of clauses 44 to 48, wherein ashape of the openings of the plurality of sections are one or more ofcircles, triangles, rectangles, squares, ellipses, hourglass shapes, andrandom perimeter openings.

Clause 50: A ureteral catheter, comprising: a drainage lumen comprisinga proximal portion configured to be positioned in at least a portion ofa patient's urethra and/or bladder and a distal portion configured to bepositioned in a patient's kidney, renal pelvis, and/or in the ureteradjacent to the renal pelvis, the distal portion comprising a coiledretention portion for maintaining positioning of the distal portion ofthe drainage lumen, the coiled retention portion comprising: at least afirst coil having a first diameter extending about an axis of theretention portion that is at least partially coextensive with a straightor curvilinear central axis of a portion of the drainage lumen proximalto the retention portion; and a plurality of sections, each of whichcomprises one or more openings on a sidewall of the retention portionfor permitting fluid flow into the drainage lumen, wherein, along theplurality of sections, the sidewall of the retention portion comprises aradially inwardly facing side and a radially outwardly facing side, andwherein a total area of the openings on the radially inwardly facingside is greater than a total area of the openings on the radiallyoutwardly facing side, and wherein a total area of openings of a firstsection of the plurality of sections is less than a total area ofopenings of an adjacent second section of the plurality of sections, thesecond section being closer to a distal end of the drainage lumen thanthe first section.

Clause 51: The ureteral catheter of clause 50, wherein the retentionportion further comprises a second coil having a second diameter, thefirst diameter being less than the second diameter, the second coilbeing closer to the distal end of the drainage lumen than the firstcoil.

Clause 52: The ureteral catheter of clause 51, wherein the first coil isa half coil extending from 0 degrees to 180 degrees and is free fromopenings, wherein the second coil is a full coil extending from 180degrees to 540 degrees, and wherein the first section of the pluralityof sections extends between 180 and 360 degrees of the second coil andthe second section extends between 360 degrees and 540 degrees of thesecond coil.

Clause 53: The ureteral catheter of clauses 51 or clause 52, wherein theretention portion further comprises a third coil extending about theaxis of the retention portion, the third coil having a diameter greaterthan or equal to either the first diameter or the second diameter, thethird coil being closer to an end of the distal portion of the drainagelumen than the second coil.

Clause 54: A ureteral catheter, comprising: a drainage lumen comprisinga proximal portion configured to be positioned in at least a portion ofa patient's urethra and/or bladder and a distal portion configured to bepositioned in a patient's kidney, renal pelvis, and/or in the ureteradjacent to the renal pelvis, the distal portion comprising a retentionportion for maintaining positioning of the distal portion of thedrainage lumen, the retention portion comprising a plurality of openingson a sidewall of the retention portion for permitting fluid flow intothe drainage lumen, wherein an area of an opening of the plurality ofopenings which is closer to a proximal end of the retention portion isless than an area of an opening of the plurality of openings which iscloser to the distal end of the drainage lumen.

Clause 55: The ureteral catheter of clause 54, wherein an area of eachopening of the plurality of openings is greater than an area of aproximally adjacent opening of the plurality of openings.

Clause 56: The ureteral catheter of clause 54 or clause 55, wherein ashape of each opening is independently selected from one or more ofcircles, triangles, rectangles, and squares.

Clause 57: A system for inducing negative pressure in a portion of aurinary tract of a patient, the system comprising: at least one ureteralcatheter comprising a drainage lumen comprising a proximal portionconfigured to be positioned in at least a portion of a patient's urethraand/or bladder and a distal portion configured to be positioned in apatient's kidney, renal pelvis, and/or in the ureter adjacent to therenal pelvis, the distal portion comprising a retention portion formaintaining positioning of the distal portion of the drainage lumen, theretention portion comprising a plurality of equal length sections of thedrainage lumen, each of which comprises one or more openings on asidewall of the drainage lumen for permitting fluid flow into thedrainage lumen; and a pump in fluid communication with the drainagelumen of the at least one ureteral catheter, the pump being configuredfor inducing a positive and/or a negative pressure in a portion of theurinary tract of the patient to draw fluid into the drainage lumenthrough the openings of the sections of the retention portion, wherein atotal area of openings of a first section of the plurality of sectionsis less than a total area of openings of an adjacent second section ofthe plurality of sections, the second section being closer to a distalend of the drainage lumen than the first section.

Clause 58: The system of clause 57, wherein the pump is configured togenerate the position and/or negative pressure in a proximal end of thedrainage lumen.

Clause 59: The system of clause 57 or clause 58, wherein the pumpapplies a negative pressure of 100 mmHg or less to a proximal end of thedrainage lumen.

Clause 60: The system of clause 59, wherein the pump is configured tooperate at one of three pressure levels selected by a user, the pressurelevels generating a negative pressure of 15 mmHg, 30 mmHg, and 45 mmHg.

Clause 61: The system of any of clauses 57 to 60, wherein the pump isconfigured to alternate between generating negative pressure andgenerating positive pressure.

Clause 62: The system of any of clauses 57 to 61, wherein the pump isconfigured to alternate between providing negative pressure andequalizing pressure to atmosphere.

Clause 63: The system of any of clauses 57 to 62, further comprising:one or more sensors in fluid communication with the drainage lumen, theone or more sensors being configured to determine information comprisingat least one of capacitance, analyte concentration, and temperature ofurine within the drainage lumen; and a controller comprising computerreadable memory including programming instructions that, when executed,cause the controller to: receive the information from the one or moresensors and adjust an operating parameter of the pump based, at least inpart, on the information received from the one or more sensors toincrease or decrease vacuum pressure in the drainage lumen of the atleast one ureteral catheter to adjust flow of urine through the drainagelumen.

Clause 64: The system of any of clauses 57 to 63, comprising a firstureteral catheter configured to be placed in a first kidney, renalpelvis, and/or in the ureter adjacent to the renal pelvis of the patientand a second ureteral catheter configured to be placed in a secondkidney, renal pelvis, and/or in the ureter adjacent to the renal pelvisof the patient, wherein the pump is configured to apply negativepressure independently to the first ureteral catheter and the secondureteral catheter such that the pressure in each catheter can be thesame or different from the other catheter.

Clause 65: The system of any of clauses 57 to 64, wherein the pump has asensitivity of 10 mmHg or less.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and characteristics of the present disclosure,as well as the methods of operation and functions of the relatedelements of structures and the combination of parts and economies ofmanufacture, will become more apparent upon consideration of thefollowing description and the appended claims with reference to theaccompanying drawings, all of which form a part of this specification,wherein like reference numerals designate corresponding parts in thevarious figures. It is to be expressly understood, however, that thedrawings are for the purpose of illustration and description only andare not intended as a definition of the limit of the invention.

Further features and other examples and advantages will become apparentfrom the following detailed description made with reference to thedrawings in which:

FIG. 1 is a schematic drawing of an indwelling portion of a urinecollection assembly deployed in a urinary tract of a patient, accordingto an example of the present invention;

FIG. 2A is a perspective view of an exemplary ureteral catheteraccording to an example of the disclosure;

FIG. 2B is a front view of the ureteral catheter of FIG. 2A;

FIG. 3A is a schematic drawing of an example of a retention portion fora ureteral catheter according to an example of the present invention;

FIG. 3B is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 3C is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 3D is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 3E is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 4A is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 4B is a schematic drawing of a cross-sectional view of a portion ofthe retention portion of FIG. 4A, taken along lines B-B of FIG. 4A;

FIG. 5A is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 5B is a schematic drawing of a portion of a cross-sectional view ofthe retention portion of FIG. 5A, taken along lines B-B of FIG. 5A;

FIG. 6 is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 7 is a schematic drawing of a cross section of another example of aretention portion for a ureteral catheter according to an example of thepresent invention;

FIG. 8 is a schematic drawing of another example of a retention portionfor a ureteral catheter according to an example of the presentinvention;

FIG. 9A is a schematic drawing of another example of a urine collectionassembly according to an example of the present invention;

FIG. 9B is a partial schematic drawing taken along section 9B-9B of thebladder anchor portion of the assembly of FIG. 9A;

FIG. 10A is a schematic drawing of another example of a urine collectionassembly according to an example of the present invention;

FIG. 10B is a schematic drawing taken along section 10B-10B of thebladder anchor portion of the assembly of FIG. 10A;

FIG. 11A is a schematic drawing of a urine collection assembly accordingto an example of the present invention;

FIG. 11B is a schematic drawing taken along section 11B-11B of a bladderanchor portion of the assembly of FIG. 11A;

FIG. 12A is a schematic drawing of another bladder anchor portion of aurine collection assembly according to an example of the disclosure;

FIG. 12B is a schematic drawing of a cross section of a bladder catheterof a urine collection assembly, taken along line C-C of FIG. 12A;

FIG. 12C is a schematic drawing of a cross section of another example ofa bladder catheter of a urine collection assembly;

FIG. 13 is a schematic drawing of another example of a bladder anchorportion of a urine collection assembly according to an example of thepresent disclosure;

FIG. 14 is a schematic drawing of another example of a bladder anchorportion of a urine collection assembly according to an example of thepresent disclosure;

FIG. 15 is a schematic drawing of another example of a bladder anchorportion of a urine collection assembly configured to be deployed in thepatient's bladder and urethra according to an example of the presentinvention;

FIG. 16 is a schematic drawing of another example of a bladder anchorportion of a urine collection assembly according to an example of thepresent invention;

FIG. 17A is an exploded perspective view of a connector for a urinecollection assembly according to an example of the disclosure;

FIG. 17B is a cross-sectional view of a portion of the connector of FIG.17A;

FIG. 17C is a schematic drawing of a connector for a urine collectionassembly according to an example of the disclosure;

FIG. 18A is a flow chart illustrating a process for insertion anddeployment of a ureteral catheter or urine collection assembly accordingto an example of the present invention;

FIG. 18B is a flow chart illustrating a process for applying negativepressure using a ureteral catheter or urine collection assemblyaccording to an example of the present invention;

FIG. 19 is a schematic drawing of a system for inducing negativepressure to the urinary tract of a patient according to an example ofthe present invention;

FIG. 20A is a plan view of a pump for use with the system of FIG. 19according to an example of the present invention;

FIG. 20B is a side elevation view of the pump of FIG. 20A;

FIG. 21 is a schematic drawing of an experimental set-up for evaluatingnegative pressure therapy in a swine model;

FIG. 22 is a graph of creatinine clearance rates for tests conductedusing the experimental set-up shown in FIG. 21;

FIG. 23A is a low magnification photomicrograph of kidney tissue from acongested kidney treated with negative pressure therapy;

FIG. 23B is a high magnification photomicrograph of the kidney tissueshown in FIG. 23A;

FIG. 23C is a low magnification photomicrograph of kidney tissue from acongested and untreated (e.g., control) kidney;

FIG. 23D is a high magnification photomicrograph of the kidney tissueshown in FIG. 23C

FIG. 24 is a flow chart illustrating a process for reducing creatinineand/or protein levels of a patient according to an example of thedisclosure;

FIG. 25 is a flow chart illustrating a process for treating a patientundergoing fluid resuscitation according to an example of thedisclosure;

FIG. 26 is a graph of serum albumin relative to baseline for testsconduct on swine using the experimental method described herein;

FIG. 27 is a schematic drawing of another example of an indwellingportion of a urine collection assembly deployed in a urinary tract of apatient, according to an example of the present invention;

FIG. 28 is another schematic drawing of the urine collection assembly ofFIG. 27;

FIG. 29 is a front view of another example of a ureteral catheteraccording to an example of the disclosure;

FIG. 30A is a perspective view of the retention portion of the ureteralcatheter of FIG. 29 enclosed by circle 30A according to an example ofthe disclosure;

FIG. 30B is a front view of the retention portion of FIG. 30A accordingto an example of the disclosure;

FIG. 30C is a rear view of the retention portion of FIG. 30A accordingto an example of the disclosure;

FIG. 30D is a top view of the retention portion of FIG. 30A according toan example of the disclosure;

FIG. 30E is a cross sectional view of the retention portion of FIG. 30Ataken along line 30E-30E according to an example of the disclosure;

FIG. 31 is a schematic drawing of a retention portion of a ureteralcatheter in a constrained or linear position according to an example ofthe disclosure;

FIG. 32 is a schematic drawing of another example of a retention portionof a ureteral catheter in a constrained or linear position according toan example of the disclosure;

FIG. 33 is a schematic drawing of another example of a retention portionof a ureteral catheter in a constrained or linear position according toan example of the disclosure;

FIG. 34 is a schematic drawing of another example of a retention portionof a ureteral catheter in a constrained or linear position according toan example of the disclosure;

FIG. 35A is a graph showing a percentage of fluid flow through openingsof an exemplary ureteral catheter as a function of position according toan example of the disclosure;

FIG. 35B is a graph showing a percentage of fluid flow through openingsof another exemplary ureteral catheter as a function of positionaccording to an example of the disclosure;

FIG. 35C is a graph showing a percentage of fluid flow through openingsof another exemplary ureteral catheter as a function of positionaccording to an example of the disclosure;

FIG. 36 is a perspective view of a tubing assembly and y-connector forconnecting a ureteral catheter to a fluid pump according to an exampleof the disclosure;

FIG. 37 is a perspective view of ureteral catheters being connected tothe y-connector of FIG. 36 according to an example of the presentdisclosure;

FIG. 38 is a schematic drawing of a retention portion of a ureteralcatheter showing “Stations” for calculating fluid flow coefficients fora mass transfer balance evaluation according to an example of thepresent disclosure; and

FIG. 39 is a schematic drawing of a nephron and surrounding vasculatureshowing a position of the capillary bed and convoluted tubules.

DETAILED DESCRIPTION

As used herein, the singular form of “a”, “an”, and “the” include pluralreferents unless the context clearly states otherwise.

As used herein, the terms “right”, “left”, “top”, and derivativesthereof shall relate to the invention as it is oriented in the drawingfigures. The term “proximal” refers to the portion of the catheterdevice that is manipulated or contacted by a user and/or to a portion ofan indwelling catheter nearest to the urinary tract access site. Theterm “distal” refers to the opposite end of the catheter device that isconfigured to be inserted into a patient and/or to the portion of thedevice that is inserted farthest into the patient's urinary tract.However, it is to be understood that the invention can assume variousalternative orientations and, accordingly, such terms are not to beconsidered as limiting. Also, it is to be understood that the inventioncan assume various alternative variations and stage sequences, exceptwhere expressly specified to the contrary. It is also to be understoodthat the specific devices and processes illustrated in the attacheddrawings, and described in the following specification, are examples.Hence, specific dimensions and other physical characteristics related tothe embodiments disclosed herein are not to be considered as limiting.

For the purposes of this specification, unless otherwise indicated, allnumbers expressing quantities of ingredients, reaction conditions,dimensions, physical characteristics, and so forth used in thespecification and claims are to be understood as being modified in allinstances by the term “about.” Unless indicated to the contrary, thenumerical parameters set forth in the following specification andattached claims are approximations that can vary depending upon thedesired properties sought to be obtained by the present invention.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements.

Also, it should be understood that any numerical range recited herein isintended to include all sub-ranges subsumed therein. For example, arange of “1 to 10” is intended to include any and all sub-ranges betweenand including the recited minimum value of 1 and the recited maximumvalue of 10, that is, all subranges beginning with a minimum value equalto or greater than 1 and ending with a maximum value equal to or lessthan 10, and all subranges in between, e.g., 1 to 6.3, or 5.5 to 10, or2.7 to 6.1.

As used herein, the terms “communication” and “communicate” refer to thereceipt or transfer of one or more signals, messages, commands, or othertype of data. For one unit or component to be in communication withanother unit or component means that the one unit or component is ableto directly or indirectly receive data from and/or transmit data to theother unit or component. This can refer to a direct or indirectconnection that can be wired and/or wireless in nature. Additionally,two units or components can be in communication with each other eventhough the data transmitted can be modified, processed, routed, and thelike, between the first and second unit or component. For example, afirst unit can be in communication with a second unit even though thefirst unit passively receives data, and does not actively transmit datato the second unit. As another example, a first unit can be incommunication with a second unit if an intermediary unit processes datafrom one unit and transmits processed data to the second unit. It willbe appreciated that numerous other arrangements are possible.

Fluid retention and venous congestion are central problems in theprogression to advanced renal disease. Excess sodium ingestion coupledwith relative decreases in excretion leads to isotonic volume expansionand secondary compartment involvement. In some examples, the presentinvention is generally directed to devices and methods for facilitatingdrainage of urine or waste from the bladder, ureter, and/or kidney(s) ofa patient. In some examples, the present invention is generally directedto devices and methods for inducing a negative pressure in the bladder,ureter, and/or kidney(s) of a patient. While not intending to be boundby any theory, it is believed that applying a negative pressure to thebladder, ureter, and/or kidney(s) can offset the medullary nephrontubule re-absorption of sodium and water in some situations. Offsettingre-absorption of sodium and water can increase urine production,decrease total body sodium, and improve erythrocyte production. Sincethe intra-medullary pressures are driven by sodium and, therefore,volume overload, the targeted removal of excess sodium enablesmaintenance of volume loss. Removal of volume restores medullaryhemostasis. Normal urine production is 1.48-1.96 L/day (or 1-1.4ml/min).

Fluid retention and venous congestion are also central problems in theprogression of prerenal Acute Kidney Injury (AKI). Specifically, AKI canbe related to loss of perfusion or blood flow through the kidney(s).Accordingly, in some examples, the present invention facilitatesimproved renal hemodynamics and increases urine output for the purposeof relieving or reducing venous congestion. Further, it is anticipatedthat treatment and/or inhibition of AKI positively impacts and/orreduces the occurrence of other conditions, for example, reduction orinhibition of worsening renal function in patients with NYHA Class IIIand/or Class IV heart failure. Classification of different levels ofheart failure are described in The Criteria Committee of the New YorkHeart Association, (1994), Nomenclature and Criteria for Diagnosis ofDiseases of the Heart and Great Vessels, (9th ed.), Boston: Little,Brown & Co. pp. 253-256, the disclosure of which is incorporated byreference herein in its entirety. Reduction or inhibition of episodes ofAKI and/or chronically decreased perfusion may also be a treatment forStage 4 and/or Stage 5 chronic kidney disease. Chronic kidney diseaseprogression is described in National Kidney Foundation, K/DOQI ClinicalPractice Guidelines for Chronic Kidney Disease: Evaluation,Classification and Stratification. Am. J. Kidney Dis. 39:S1-S266, 2002(Suppl. 1), the disclosure of which is incorporated by reference hereinin its entirety.

Systems for Inducing Negative Pressure

With reference to FIG. 27, an exemplary system 1100 for inducingnegative pressure in a urinary tract of a patient for increasing renalperfusion is illustrated. The system 1100 comprises one or two ureteralcatheters 1212 connected to a fluid pump 2000 for generating thenegative pressure. In some examples, the pump 2000 may also generate apositive pressure and, for example, may be configured to alternatebetween providing negative pressure, positive pressure, and equalizingpressure to atmosphere based on a selection from a user or automaticallyaccording to a predetermined schedule. The pump 2000 can be configuredto provide a low level negative pressure of 100 mmHg or less to aproximal end of the catheter 1212. In some examples, the pump 2000 canbe configured to operate at a number of discrete pressure levels. Forexample, the pump 2000 may be configured to operate at pressure levelsof 15 mmHg, 30 mmHg, and 45 mmHg. A user can select one of the pressurelevels using a switch, dial, or controller as are known in the art.

A commercially available pump which can be adapted for use with thesystem 1100 is the Air Cadet Vacuum Pump from Cole-Partner InstrumentCompany (Model No. EW-07530-85). The pump 2000 can be connected inseries to the regulator, such as the V-800 Series Miniature PrecisionVacuum Regulator—⅛ NPT Ports (Model No. V-800-10-W/K), manufactured byAirtrol Components Inc. Pumps which can be adapted for use with thesystem 2000 are also available from Ding Hwa Co., Ltd (DHCL Group) ofDacun, Changhua, China.

In some examples, at least a portion of the pump 2000 can be positionedwithin the patient's urinary tract, for example within the bladder. Forexample, the pump 2000 can comprise a pump module and a control modulecoupled to the pump module, the control module being configured todirect motion of the pump module. At least one (one or more) of the pumpmodule, the control module, or the power supply may be positioned withinthe patient's urinary tract. The pump module can comprise at least onepump element positioned within the fluid flow channel to draw fluidthrough the channel. Some examples of suitable pump assemblies, systemsand methods of use are disclosed in U.S. Patent Application No.62/550,259, entitled “Indwelling Pump for Facilitating Removal of Urinefrom the Urinary Tract”, filed concurrently herewith, which isincorporated by reference herein in its entirety.

The patient's urinary tract comprises the patient's right kidney 2 andleft kidney 4. The kidneys 2, 4 are responsible for blood filtration andclearance of waste compounds from the body through urine. Urine producedby the right kidney 2 and the left kidney 4 is drained into a patient'sbladder 10 through tubules, namely a right ureter 6 and a left ureter 8,which are connected to the kidneys at the renal pelvis 20, 21. Urine maybe conducted through the ureters 6, 8 by peristalsis of the ureterwalls, as well as by gravity. The ureters 6, 8 enter the bladder 10through a ureter orifice or opening 16. The bladder 10 is a flexible andsubstantially hollow structure adapted to collect urine until the urineis excreted from the body. The bladder 10 is transitionable from anempty position (signified by reference line E) to a full position(signified by reference line F). Normally, when the bladder 10 reaches asubstantially full state, urine is permitted to drain from the bladder10 to a urethra 12 through a urethral sphincter or opening 18 located ata lower portion of the bladder 10. Contraction of the bladder 10 can beresponsive to stresses and pressure exerted on a trigone region 14 ofthe bladder 10, which is the triangular region extending between theureteral openings 16 and the urethral opening 18. The trigone region 14is sensitive to stress and pressure, such that as the bladder 10 beginsto fill, pressure on the trigone region 14 increases. When a thresholdpressure on the trigone region 14 is exceeded, the bladder 10 begins tocontract to expel collected urine through the urethra 12.

As shown in FIGS. 27 and 28, distal portions of the ureteral catheter(s)are deployed in the renal pelvis 20, 21 near the kidneys 2, 4. Proximalportions of one or more of the catheter(s) 1212 are connected to asingle outflow port 2002 of a fluid pump 2000 through a Y-connector 2010and tubing set 2050. An exemplary Y-connector 2010 and tubing set 2020connected thereto are shown in FIGS. 36 and 37. The Y-connector 2010comprises a tubular body 2012 formed from a rigid plastic material, thebody 2012 comprising two inflow ports 2014, 2016 and a single outflowport comprising a one-way check valve 2018 to prevent backflow. Theinflow ports 2014, 2016 can comprise a connector portion 2020, such as aluer lock connector, screw connector, or similar mechanism as is knownin the art for receiving the proximal end of the catheters 1212. Asshown in FIG. 37, the proximal ends of catheters 1212 have acorresponding structure for mounting to the Y-connector 2010. The tubingset 2050 comprises a length of flexible medical tubing 2052 extendingbetween the one-way check valve 2018 of the Y-connector 2010 and afunnel-shaped connector 2054 configured to engage the outflow port 2002of a fluid pump 2000. The shape and size of the funnel-shaped connector2054 can be selected based on the type of pump 2000 being used. In someexamples, the funnel-shaped connector 2054 can be manufactured with adistinctive configuration so that it can only be connected to aparticular pump type, which is deemed to be safe for inducing negativepressure in a patient's bladder, ureter, or kidneys. In other examples,as described herein, the connector 2054 can be a more genericconfiguration adapted for attachment to a variety of different types offluid pumps.

System 1100 is but one example of a negative pressure system forinducing negative pressure that can be used with the ureteral catheters1212 disclosed herein. Other systems and urine collection assemblieswhich can be used with catheters 1212 are shown, for example, in FIGS.1, 9A, 10A, 11A, and 19. In addition, catheter(s) 1212 can be connectedto separate sources of negative pressure. In other examples, one or morecatheter(s) 1212 can be connected to a negative pressure source, whileother caterer(s) 1212 can be connected to an unpressurized fluidcollection container.

Exemplary Ureteral Catheters:

Specific characteristics of exemplary ureteral catheters will now bedescribed in detail. As shown in FIGS. 27-39D, an exemplary ureteralcatheter 1212 comprises at least one elongated body or tube 1222, theinterior of which defines or comprises one or more drainage channel(s)or lumen(s), such as drainage lumen 1224. The tube 1222 size can rangefrom about 1 Fr to about 9 Fr (French catheter scale). In some examples,the tube 1222 can have an external diameter ranging from about 0.33 toabout 3.0 mm and an internal diameter ranging from about 0.165 to about2.39 mm. In one example, the tube 1222 is 6 Fr and has an outer diameterof 2.0±0.1 mm. The length of the tube 1222 can range from about 30 cm toabout 120 cm depending on the age (e.g., pediatric or adult) and genderof the patient.

The tube 1222 can be formed from a flexible and/or deformable materialto facilitate advancing and/or positioning the tube 1222 in the bladder10 and ureters 6, 8 (shown in FIGS. 27 and 28). For example, the tube1222 can be formed from materials including biocompatible polymers,polyvinyl chloride, polytetrafluoroethylene (PTFE) such as Teflon®,silicone coated latex, or silicone. In one example, the tube 1222 isformed from a thermoplastic polyurethane. The tube 1222 can also includeor be impregnated with one or more of copper, silver, gold,nickel-titanium alloy, stainless steel, and titanium. In some examples,the tube 1222 is impregnated with or formed from a material viewable byfluoroscopic imaging. In other examples, the biocompatible polymer whichforms the tube 1222 can be impregnated with barium sulfate or a similarradiopaque material. As such, the structure and position of the tube1222 is visible to fluoroscopy.

In some examples, the drainage lumen 1224 defined by tube 1222comprises: a distal portion 1218 (e.g., a portion of the tube 1222configured to be positioned in the ureter 6, 8 and renal pelvis 20, 21(shown in FIGS. 27-29)); a middle portion 1226 (e.g., a portion of thetube 1222 configured to extend from the distal portion through ureteralopenings 16 into the patient's bladder 10 and urethra 12 (shown in FIGS.27-29)); and a proximal portion 1228 (e.g., a portion of the tube 1222extending from the urethra 12 to an external fluid collection containerand/or pump 2000). In one preferred example, the combined length of theproximal portion 1228 and the middle portion 1226 of the tube 1222 isabout 54±2 cm. In some examples, the middle portion 1226 and proximalportion 1228 of the tube 1222 includes distance markings 1236 (shown inFIG. 29) on a sidewall of the tube 1222 which can be used, duringdeployment of the catheter 1212, to determine how far the tube 1222 isinserted into the urinary tract of the patient.

In some examples, the distal portion 1218 comprises an open distal end1220 for drawing fluid into the drainage lumen 1224. The distal portion1218 of the ureteral catheter 1212 further comprises a retention portion1230 for maintaining the distal portion 1218 of the drainage lumen ortube 1222 in the ureter and/or kidney. In some examples, the retentionportion comprises a plurality of radially extending coils 1280, 1282,1284. The retention portion 1230 can be a flexible and bendable topermit positioning of the retention portion 1230 in the ureter, renalpelvis, and/or kidney. For example, the retention portion 1230 isdesirably sufficiently bendable to absorb forces exerted on the catheter1212 and to prevent such forces from being translated to the ureters.Further, if the retention portion 1230 is pulled in the proximaldirection P (shown in FIGS. 27 and 28) toward the patient's bladder 10,the retention portion 1230 can be sufficiently flexible to begin tounwind or be straightened so that it can be drawn through the ureter 6,8. In some examples, the retention portion 1230 is integral with thetube 1222. In other examples, the retention portion 1230 can comprise aseparate tubular member connected to and extending from the tube ordrainage lumen 1224. In some examples, the catheter 1212 comprises aradiopaque band 1234 (shown in FIG. 29) positioned on the tube 1222 at aproximal end of the retention portion 1230. The radiopaque band 1234 isvisible by fluoroscopic imaging during deployment of the catheter 1212.In particular, a user can monitor advancement of the band 1234 throughthe urinary tract by fluoroscopy to determine when the retention portion1230 is in the renal pelvis and ready for deployment.

In some examples, the retention portion 1230 comprises perforations,drainage ports, or openings 1232 (shown in FIG. 30A) in a sidewall ofthe tube 1222. As used herein, “opening” or “hole” means a continuousvoid space or channel through the sidewall from the outside to theinside of the sidewall, or vice versa. In some examples, each of the atleast one opening(s) can have an area which can be the same or differentand can range from about 0.002 mm² to about 100 mm², or about 0.002 mm²to about 10 mm². As used herein, the “area” or “surface area” or“cross-sectional area” of an opening means the smallest or minimumplanar area defined by a perimeter of the opening. For example, if theopening is circular and has a diameter of about 0.36 mm (area of 0.1mm²) at the outside of the sidewall, but a diameter of only 0.05 mm(area of 0.002 mm²) at some point within the sidewall or on the oppositeside of the sidewall, then the “area” would be 0.002 mm² since that isthe minimum or smallest planar area for flow through the opening in thesidewall. If the hole is square or rectangular, the “area” would be thelength times the width of the planar area. For any other shapes, the“area” can be determined by conventional mathematical calculations wellknown to those skilled in the art. For example, the “area” of anirregular shaped opening is found by fitting shapes to fill the planararea of the opening, calculating the area of each shape and addingtogether the area of each shape.

Openings 1232 can be positioned extending along on a sidewall of thetube 1222 in any direction desired, such as longitudinal and/or axial.In some examples, spacing between the openings 1232 can range from about1.5 mm to about 15 mm. Fluid passes through one or more of theperforations, drainage ports, or openings 1232 and into the drainagelumen 1234. Desirably, the openings 1232 are positioned so that they arenot occluded by tissues of the ureters 6, 8 or kidney when negativepressure is applied to the drainage lumen 1224. For example, asdescribed herein, openings 1234 can be positioned on interior portionsof coils or other structures of the retention portion 1230 to avoidocclusion of the openings 1232. In some examples, the middle portion1226 and proximal portion 1228 of the tube 1222 can be essentially freeof or free from perforations, ports, holes or openings to avoidocclusion of openings along those portions of the tube 1222. In someexamples, a portion 1226, 1228 which is essentially free fromperforations or openings includes substantially fewer openings thanother portions of the tube 1222. For example, a total area of openings1232 of the distal portion 1218 may be greater than or substantiallygreater than a total area of openings of the proximal portion 1226and/or the distal portion 1228 of the tube 1222.

In some examples, the openings 1232 are sized and spaced to improvefluid flow through the retention portion 1230. In particular, thepresent inventors have discovered that when a negative pressure isapplied to the drainage lumen 1224 of the catheter 1212 a majority offluid is drawn into the drainage lumen 1224 through proximal-mostperforations or openings 1232. In order to improve flow dynamics so thatfluid is also received through more distal openings and/or through theopen distal end 1220 of the tube 1222, larger size or a greater numberof openings can be provided toward the distal end of the retentionportion 1230. For example, a total area of openings 1232 on a length oftube 1222 near a proximal end of the retention portion 1230 may be lessthan a total area of openings 1232 of a similar sized length of the tube1222 located near the open distal end 1220 of the tube 1222. Inparticular, it may be desirable to produce a flow distribution throughthe drainage lumen 1224 in which less than 90%, preferably less than70%, and, more preferably, less than 55% of fluid flow is drawn into thedrainage lumen 1224 through a single opening 1232 or a small number ofopenings 1232 positioned near the proximal end of the retention portion1230.

In many examples, the openings 1232 are generally a circular shape,though triangular, elliptical, square, diamond, and any other openingshapes may also be used. Further, as will be appreciated by one ofordinary skill in the art, a shape of the openings 1232 may change asthe tube 1222 transitions between an uncoiled or elongated position anda coiled or deployed position. It is noted that while the shape of theopenings 1232 may change (e.g., the orifices may be circular in oneposition and slightly elongated in the other position), the area of theopenings 1232 is substantially similar in the elongated or uncoiledposition compared to the deployed or coiled position.

Helical Coil Retention Portion

Referring now to FIGS. 30A-30E, an exemplary retention portion 1230comprises helical coils 1280, 1282, 1284. In some examples, theretention portion 1230 comprises a first or half coil 1280 and two fullcoils, such as a second coil 1282 and a third coil 1284. As shown inFIGS. 30A-30D, in some examples, the first coil comprises a half coilextending from 0 degrees to 180 degrees around a curvilinear centralaxis A of the retention portion 1230. In some examples, as shown thecurvilinear central axis A is substantially straight and co-extensivewith a curvilinear central axis of the tube 1222. In other examples, thecurvilinear central axis A of the retention portion 1230 can be curvedgiving the retention portion 1230 a cornucopia shape. The first coil1280 can have a diameter D1 of about 1 mm to 20 mm and preferably about8 mm to 10 mm. The second coil 1282 can be a full coil extending from180 degrees to 540 degrees along the retention portion 1230 having adiameter D2 of about 5 mm to 50 mm, preferably about 10 mm to 20 mm, andmore preferably about 14 mm±2 mm. The third coil 1284 can be a full coilextending between 540 degrees and 900 degrees and having a diameter D3of between 5 mm and 60 mm, preferably about 10 mm to 30 mm, and morepreferably about 18 mm±2 mm. In other examples, multiple coils 1282,1284 can have the same inner and/or outer diameter. For example, anouter diameter of the full coils 1282, 1284, can each be about 18±2 mm.

In some examples, an overall height H1 of the retention portion 1230ranges from about 10 mm to about 30 mm and, preferably about 18±2 mm. Aheight H2 (shown in FIG. 30E) of a gap between coils 1284, namelybetween the sidewall of the tube 1222 of the first coil 1280 and theadjacent sidewall of the tube 122 of the second coil 1282 is less than3.0 mm, preferably between about 0.25 mm and 2.5 mm, and more preferablybetween about 0.5 mm and 2.0 mm.

The retention portion 1230 can further comprise a distal-most curvedportion 1290. For example, the distal most portion 1290 of the retentionportion 1230, which includes the open distal end 1220 of the tube 1222,can be bent inwardly relative to a curvature of the third coil 1284. Forexample, a curvilinear central axis X1 (shown in FIG. 30D) of thedistal-most portion 1290 can extend from the distal end 1220 of the tube1222 toward the curvilinear central axis A of the retention portion1230.

The retention portion 1230 is capable of moving between a contractedposition, in which the retention portion 1230 is straight for insertioninto the patient's urinary tract, and the deployed position, in whichthe retention portion 1230 comprises the helical coils 1280, 1282, 1284.Generally, the tube 1222 is naturally biased toward the coiledconfiguration. For example, an uncoiled or substantially straightguidewire can be inserted through the retention portion 1230 to maintainthe retention portion 1230 in its straight contracted position, as shownfor example in FIGS. 31-35. When the guidewire is removed, the retentionportion 1230 naturally transitions to its coiled position.

In some examples, the openings 1232 are disposed essentially only oronly on a radially inwardly facing side 1286 of the coils 1280, 1282,1284 to prevent occlusion or blockage of the openings 1232. A radiallyoutwardly facing side 1288 of the coils 1280, 1282, 1284 may beessentially free of the openings 1232. In similar examples, a total areaof openings 1232 on the inwardly facing side 1286 of the retentionportion 1230 can be substantially greater than a total area of openings1232 on the radially outwardly facing side 1288 of the retention portion1230. Accordingly, when negative pressure is induced in the ureterand/or renal pelvis, mucosal tissue of the ureter and/or kidney may bedrawn against the retention portion 1230 and may occlude some openings1232 on the outer periphery of the retention portion 1230. However,openings 1232 located on the radially inward side 1286 of the retentionportion 1230 are not appreciably occluded when such tissues contact theouter periphery of the retention portion 1230. Therefore, risk of injuryto the tissues from pinching or contact with the drainage openings 1232can be reduced or eliminated.

Hole or Opening Distribution Examples

In some examples, the first coil 1280 can be free or essentially freefrom openings. For example, a total area of openings on the first coil1280 can be less than or substantially less than a total area ofopenings of the full coils 1282, 1284. Examples of various arrangementsof holes or openings which could be used for a coiled retention portion(such as coiled retention portion 1230 shown in FIGS. 30A-30E), areillustrated in FIGS. 31-34. As shown in FIGS. 31-34, a retention portionis depicted in its uncoiled or straight position, as occurs when aguidewire is inserted through the drainage lumen.

An exemplary retention portion 1330 is illustrated in FIG. 31. In orderto more clearly describe positioning of openings of the retentionportion 1330, the retention portion 1330 is referred to herein as beingdivided into a plurality of sections or perforated sections, such as aproximal-most or first section 1310, a second section 1312, a third,section 1314, a fourth section 1316, a fifth section 1318, and adistal-most or sixth section 1320. One of ordinary skill in the artwould understand that additional sections can be included, if desired.As used herein, “section” refers to a discrete length of the tube 1322within the retention portion 1330. In some examples, sections are equalin length. In other examples, some sections can have the same length,and other sections can have a different length. In other examples, eachsection has a different length. For example, sections can have a lengthL1-L6 of between about 5 mm and about 35 mm, and preferably betweenabout 5 mm and 15 mm.

In some examples, each section comprises one or more openings. In someexamples, each section each comprises a single opening 1332. In otherexamples, the first section 1310 includes a single opening 1332 andother sections comprise multiple openings 1332. In other examples,different sections comprise one or more openings 1332, each of theopening(s) having a different shape or different total area.

In some examples, such as the retention portion 1230 shown in FIGS.30A-30E, the first or half coil 1280, which extends from 0 to about 180degrees of the retention portion 1230 can be free from or essentiallyfree from openings. The second coil 1282 can include the first section1310 extending between about 180 and 360 degrees. The second coil 1282can also include the second and third sections 1312, 1314 positionedbetween about 360 degrees and 540 degrees of the retention portion 1230.The third coil 1284 can include the fourth and fifth sections 1316, 1318positioned between about 540 degrees and 900 degrees of the retentionportion 1230.

In some examples, the openings 1332 can be sized such that a total areaof openings of the first section 1310 is less than a total area ofopenings of the adjacent second section 1312. In a similar manner, ifthe retention portion 1330 further comprises a third section 1314, thenopenings of a third section 1314 can have a total area that is greaterthan the total area of the openings of the first section 1310 or thesecond section 1312. Openings of the fourth 1316, fifth 1318, and sixth1320 sections may also have a gradually increasing total area and/ornumber of openings to improve fluid flow through the tube 1222.

As shown in FIG. 31, the retention portion 1230 of the tube includesfive sections 1310, 1312, 1314, 1316, 1318 each of which includes asingle opening 1332, 1334, 1336, 1338, 1340. The retention portion 1230also includes a sixth section 1320 which includes the open distal end1220 of the tube 1222. In this example, the opening 1332 of the firstsection 1310 has the smallest total area. For example, a total area ofthe opening 1332 of the first section can be between about 0.002 mm² andabout 2.5 mm², or between about 0.01 mm² and 1.0 mm², or between about0.1 mm² and 0.5 mm². In one example, the opening 1332 is about 55 mmfrom the distal end 1220 of the catheter, has a diameter of 0.48 mm, andan area of about 0.18 mm². In this example, a total area of an opening1334 of the second section 1312 is greater than the total area of anopening 1332 of the first section 1310 and can range in size from about0.01 mm² and 1.0 mm². The third 1336, fourth 1338, and fifth 1350openings can also range in size from about 0.01 mm² and 1.0 mm². In oneexample, the second opening 1334 is about 45 mm from the distal end ofthe catheter 1220, has a diameter of about 0.58 mm, and an area of about0.27 mm². The third opening 1336 can be about 35 mm from the distal endof the catheter 1220 and have a diameter of about 0.66 mm. The fourthopening 1338 can be about 25 mm from the distal end 1220 and have adiameter of about 0.76 mm. The fifth opening 1340 can be about 15 mmfrom the distal end 1220 of the catheter and have a diameter of about0.889 mm. In some examples, the open distal end 1220 of the tube 1222has the largest opening having an area of between about 0.5 mm² to about5.0 mm² or more. In one example, the open distal end 1220 has a diameterof about 0.97 mm and an area of about 0.74 mm².

As described herein, openings 1332, 1334, 1336, 1338, 1340 can bepositioned and sized so that a volumetric flow rate of fluid passingthrough the first opening 1332 more closely corresponds to a volumetricflow rate of openings of more distal sections when negative pressure isapplied to the drainage lumen 1224 of the catheter 1212. As describedabove, if each opening were the same area, then when negative pressureis applied to the drainage lumen 1224, the volumetric flow rate of fluidpassing through the proximal-most of first opening 1332 would besubstantially greater than a volumetric flow rate of fluid passingthrough openings 1334 closer to the distal end 1220 of the retentionportion 1330. While not intending to be bound by any theory, it isbelieved that when negative pressure is applied, the pressuredifferential between the interior of the drainage lumen 1224 andexternal to the drainage lumen 1224 is greater in the region of theproximal-most opening and decreases at each opening moving toward thedistal end of the tube. For example, sizes and positions of the openings1332, 1334, 1336, 1338, 1340 can be selected so that a volumetric flowrate for fluid which flows into openings 1334 of the second section 1312is at least about 30% of a volumetric flow rate of fluid which flowsinto the opening(s) 1332 of the first section 1310. In other examples, avolumetric flow rate for fluid flowing into the proximal-most or firstsection 1310 is less than about 60% of a total volumetric flow rate forfluid flowing through the proximal portion of the drainage lumen 1224.In other examples, a volumetric flow rate for fluid flowing intoopenings 1332, 1334 of the two proximal-most sections (e.g., the firstsection 1310 and the second section 1312) can be less than about 90% ofa volumetric flow rate of fluid flowing through the proximal portion ofthe drainage lumen 1224 when a negative pressure, for example a negativepressure of about −45 mmHg, is applied to the proximal end of thedrainage lumen.

As will be appreciated by one of ordinary skill in the art, volumetricflow rate and distribution for a catheter or tube comprising a pluralityof openings or perforations can be directly measured or calculated in avariety of different ways. As used herein, “volumetric flow rate” meansactual measurement of the volumetric flow rate downstream and adjacentto each opening or using a method for “Calculated Volumetric Flow Rate”described below.

For example, actual measurement of the dispersed fluid volume over timecan be used to determine the volumetric flow rate through each opening1332, 1334, 1336, 1338, 1340. In one exemplary experimental arrangementof an ex vivo test of dispersed fluid volume, a multi-chamber vessel,such as a sleeve or box, comprising individual chambers sized to receivesections 1310, 1312, 1314, 1316, 1318, 1320 of the retention portion1330 could be sealed around and enclose the retention portion 1330. Eachopening 1332, 1334, 1336, 1338, 1340 could be sealed in one of thechambers. In this arrangement, each chamber encloses an identical volumeand is filled with an equal amount of fluid, such that an initial fluidpressure within each chamber is identical. Experimental conditions maybe selected to be similar to fluid collection conditions in the body.For example, a temperature of 37° C. may be used and the chambers may befilled with urine having an approximate density of 1.03 g/mL and had acoefficient of friction μ of 8.02×10−3 Pa·S (8.02×10−3 kg/s·m). Negativepressure of 100 mmHg or less can be applied to a proximal end of thecatheter tube for fluid collection. In some examples, a negativepressure of −15 mmHg, −30 mmHg, or −45 mmHg is applied.

An amount of fluid volume drawn from the respective chambers into thetube 3222 through each opening 1332, 1334, 1336, 1338, 1340 could bemeasured to determine an amount of fluid volume drawn into each openingover time when a negative pressure is applied. For example, each chambermay be initially filled with a predetermined fluid volume of, forexample, 100 mL of urine. Negative pressure can be applied by a pump fora predetermined period of time, such as 30 seconds, 1 minute, 5 minutes,or 15 minutes. After the predetermined period of time, the pump can beshut off and the fluid remaining in each chamber can be measured. Adifference between the measured fluid remaining and the initial fluidamount corresponds to an amount of fluid drawn into the drainage lumenof the tube through each opening. The cumulative amount of fluid volumecollected in the tube 1222 by a negative pressure pump system would beequivalent to the sum of fluid drawn into each opening 1332, 1334, 1336,1338, 1340.

Alternatively, volumetric fluid flow rate through different openings1332, 1334, 1336, 1338, 1340 can be calculated mathematically usingequations for modeling fluid flow through a tubular body. For example,volumetric flow rate of fluid passing through openings 1332, 1334, 1336,1338, 1340 and into the drainage lumen 1224 can be calculated based on amass transfer shell balance evaluation, as described in detail below inconnection with the Mathematical Examples and FIGS. 35A-35C. Steps forderiving mass balance equations and for calculating a flow distributionbetween or volumetric flow rates for the openings 1332, 1334, 1336,1338, 1340 are also described in detail below in connection with FIGS.35A-35C.

Another exemplary retention portion 2230 with openings 2332, 2334, 2336,2338, 2340 is illustrated in FIG. 32. As shown in FIG. 32, the retentionportion 2230 comprises numerous smaller perforations or openings 2332,2334, 2336, 2338, 2340. Each of the openings 2332, 2334, 2336, 2338,2340 can have a substantially identical minimum area through thesidewall of the tube 2222. As shown in FIG. 32, the retention portion2330 comprises six sections 2310, 2312, 2314, 2316, 2318, 2320, such asare described above, wherein each section comprises a plurality of theopenings 2332, 2334, 2336, 2338, 2340. In the example shown in FIG. 32,a number of openings 2332, 2334, 2336, 2338, 2340 per section increasestoward the distal end 2220 of the tube 1222, such that a total area ofopenings 1332 in each section increases compared to a proximallyadjacent section.

As shown in FIG. 32, openings 2332 of the first section 2310 arearranged along a first virtual line V1, which is substantially parallelto a curvilinear central axis X1 of the retention portion 2230. Openings2334, 2336, 2338, 2340 of the second 2312, third 2314, fourth 2316, andfifth 2318 sections, respectively, are positioned on the sidewall of thetube 2222 in a gradually increasing number of rows, such that openings2334, 2336, 2338, 2340 of these sections also line up around acircumference of the tube 2222. For example, some of the openings 2334of the second section 2312 are positioned such that a second virtualline V2 extending around a circumference of the sidewall of the tube2222 contacts at least a portion of multiple openings 2334. For example,the second section 2312 can comprise two or more rows of perforations oropenings 2334, in which each opening 2334 has an equal minimum area.Further, in some examples, at least one of the rows of the secondsection 2312 can be aligned along a third virtual line V3, which isparallel with the curvilinear central axis X1 of the tube 2222, but isnot co-extensive with the first virtual line V1. In a similar manner,the third section 2314 can comprise five rows of perforations oropenings 2336, in which each opening 2336 has an equal minimum area; thefourth section 2316 can comprise seven rows of perforations or openings2338; and the fifth section 2318 can comprise nine rows of perforationsor openings 2340. As in previous examples, the sixth section 2320comprises a single opening, namely, the open distal end 2220 of the tube2222. In the example of FIG. 32, each of the openings has the same area,although the area of one or more openings can be different if desired.

Another exemplary retention portion 3230 with openings 3332, 3334, 3336,3338, 3340 is illustrated in FIG. 33. The retention portion 3230 of FIG.33 includes a plurality of similarly sized perforations or openings3332, 3334, 3336, 3338, 3340. As in previous examples, the retentionportion 3230 can be divided into six sections 3310, 3312, 3314, 3316,3318, 3320, each of which comprises at least one opening. Theproximal-most or first section 3310 includes one opening 3332. Thesecond section 3312 includes two openings 3334 aligned along the virtualline V2 extending around a circumference of the sidewall of the tube3222. The third section 3314 comprises a grouping of three openings3336, positioned at vertices of a virtual triangle. The fourth section3316 comprises a grouping of four openings 3338 positioned at corners ofa virtual square. The fifth section 3318 comprises ten openings 3340positioned to form a diamond shape on the sidewall of the tube 3222. Asin previous examples, the sixth section 3320 comprises a single opening,namely, the open distal end 3220 of the tube 3222. The area of eachopening can range from about 0.002 mm² and about 2.5 mm².

Another exemplary retention portion 4230 with openings 4332, 4334, 4336,4338, 4340 is illustrated in FIG. 34. The openings 4332, 4334, 4336,4338, 4340 of the retention portion 4330 have different shapes andsizes. For example, the first section 4310 includes a single circularopening 4332. The second section 4312 has a circular opening 4334 with alarger cross-sectional area than the opening 4332 of the first section4310. The third section 4314 comprises three triangular-shaped openings4336. The fourth section 4316 comprises a large circular opening 4338.The fifth section 4318 comprises a diamond-shaped opening 4340. As inprevious examples, the sixth section 4320 comprises the open distal end4220 of the tube 4222. FIG. 34 illustrates one example of an arrangementof different shapes of openings in each section. It is understood thatthe shape of each opening in each section can be independently selected,for example the first section 4310 can have one or more diamond-shapedopenings or other shapes. The area of each opening can range from about0.002 mm² and about 2.5 mm².

EXAMPLES

Calculation of Volumetric Flow Rate and Percentage of Flow Distribution

Having described various arrangements of openings for retention portionsof the ureteral catheter 1212, a method for determining the CalculatedPercentage of Flow Distribution and Calculated Volumetric Flow Ratethrough the catheter will now be described in detail. A schematicdrawing of an exemplary catheter with sidewall openings showing aposition of portions of the tube or drainage lumen used in the followingcalculations is shown in FIG. 38. Calculated Percentage of FlowDistribution refers to a percentage of total fluid flowing throughproximal portions of the drainage lumen which enters the drainage lumenthrough different openings or sections of the retention portion.Calculated Volumetric Flow rate refers to fluid flow per unit timethrough different portions of the drainage lumen or openings of theretention portion. For example, a volumetric flow rate for a proximalportion of the drainage lumen describes a rate of flow for a totalamount of fluid passing through the catheter. A volumetric flow rate foran opening refers to a volume of fluid which passes through the openingand into the drainage lumen per unit time. In Tables 3-5 below flow isdescribed as a percentage of total fluid flow or of a total volumetricflow rate for a proximal portion of the drainage lumen. For example, anopening having a flow distribution of 100% means that all fluid enteringthe drainage lumen passed through the opening. An opening having adistribution of 0% would indicate that none of the fluid in the drainagelumen entered the drainage lumen through that opening.

These volumetric flow rate calculations were used to determine and modelfluid flow through the retention portion 1230 of the ureter catheter1212 shown in FIGS. 27-34. Further, these calculations show thatadjusting the area of openings and linear distribution of openings alongthe retention portion affects a distribution of fluid flow throughdifferent openings. For example, reducing the area of the proximal-mostopening decreases the proportion of fluid drawn into the catheterthrough the proximal most opening and increases the proportion of fluiddrawn into more distal openings of the retention portion.

For the following calculations, a tube length of 86 cm having an innerdiameter of 0.97 mm and an end hole inner diameter of 0.97 mm was used.Density of urine was 1.03 g/mL and had a coefficient of friction μ of8.02×10−3 Pa·S (8.02×10−3 kg/s·m) at 37° C. The urine volumetric flowrate passing through the catheter was 2.7 ml per minute (Q_(Total)) asdetermined by experimental measurement.

Calculated Volumetric Flow Rate is determined by a volumetric massbalance equation in which a sum total of volumetric flow through allperforations or openings 1232 of the five sections of the retentionportion (referred to herein as volumetric flow Q₂ to Q₆) and through theopen distal end 1220 (referred to herein as volumetric flow Q₁) equalsthe total volumetric flow (Q_(Total)) exiting the proximal end of thetube 1222 at a distance of 10 cm to 60 cm away from the last proximalopening, as shown in Equation 2.

Q _(Total) =Q ₁ +Q ₂ +Q ₃ +Q ₄ +Q ₅ +Q ₆  (Equation 2)

A Modified Loss Coefficient (K′) for each of the sections is based onthree types of loss coefficients within the catheter model, namely: anInlet Loss Coefficient taking into account a pressure loss resulting ata pipe inlet (e.g., the openings and open distal end of the tube 1222);a Friction Loss Coefficient which takes into account pressure lossresulting from friction between the fluid and pipe wall; and a FlowJunction Loss Coefficient taking into account pressure loss resultingfrom the interaction of two flows coming together.

The Inlet Loss Coefficient is dependent on a shape of the orifice oropening. For example, a tapered or nozzle shaped orifice would increaseflow rate into the drainage lumen 1224. In a similar manner, asharp-edged orifice would have different flow properties than an orificewith less defined edges. For purposes of the following calculations, itis assumed that the openings 1232 are side orifice openings and the opendistal end 1220 of the tube 1222 is a sharp-edged opening. The crosssectional area of each opening is considered constant through the tubesidewall.

The Friction Loss Coefficient approximates pressure loss resulting fromfriction between the fluid and the adjacent inner wall of the tube 1222.Friction loss is defined according to the following equations:

$\begin{matrix}{{Re} = \frac{\rho\;{UD}}{\mu}} & \left( {{Equation}\mspace{14mu} 3.1} \right) \\{f = \frac{c_{f}}{Re}} & \left( {{Equation}\mspace{14mu} 3.2} \right) \\{K_{1 - 2} = {K_{2 - 3} = {K_{3 - 3} = {K_{4 - 3} = {K_{5 - 3} = {K_{f} = {f\frac{L}{D}}}}}}}} & \left( {{Equation}\mspace{14mu} 3.3} \right)\end{matrix}$

The Flow Junction Loss Coefficients are derived from loss coefficientsfor combining flow at a branch angle of 90 degrees. Values for the losscoefficients were obtained from Charts 13.10 and 13.11 of Miller DS,Internal Flow Systems, 1990, incorporated by reference herein. Thecharts use the ratio of the inlet orifice area (referred to as A1 in thecharts) to the pipe cross-sectional area (referred to as A3 in thecharts) and the ratio of the inlet orifice volumetric flow rate (Q1 inthe charts) to the resulting combined pipe volumetric flow rate (Q3 inthe charts). For example, for an area ratio of 0.6 between an area ofthe opening and an area of the drainage lumen, the following FlowJunction Loss Coefficients (K₁₃ and K₂₃) would be used.

Flow Ratio (Q₁/Q₃) 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 K₁₃ −0.58−0.04 0.11 0.45 0.75 1.13 1.48 1.81 2.16 2.56 K₂₃ 0.15 0.27 0.39 0.480.56 0.63 0.69 0.72 0.74 0.76

To calculate the Total Manifold Loss Coefficient (K), it is necessary toseparate the model into so-called “reference stations” and progressivelywork through and balance the pressure and flow distributions of the twopaths (e.g., flow through the opening and flow through the drainagelumen of the tube) to reach each station starting from the distal tip tothe most proximal “Station”. A graphical representation of the differentstations used for this calculation is shown in FIG. 38. For example, amost-distal “Station” A is the distal open end 1220 of the tube 122. Asecond Station A′ is the distal most opening on the sidewall of the tube122 (e.g., the opening(s) of the fifth section 1318 in FIGS. 31-34). Thenext station B is for flow through the drainage lumen 1224 just proximalto the A′ opening.

To calculate loss between Station A (the distal opening) and Station Bfor fluid entering through the open distal end of the tube 1222 (Path1), the modified loss coefficient (K′) is equal to:

$\begin{matrix}{K^{\prime} = {{{Inlet}\mspace{14mu}{Loss}} + {{Friction}\mspace{14mu}{Loss}} + {{Flow}\mspace{14mu}{Junction}\mspace{14mu}{Loss}}}} & \left( {{Equation}\mspace{14mu} 5.1} \right) \\{K_{B}^{\prime} = {{K_{1 - 1} \times \left( {\frac{A_{Pipe}}{A_{1}} \times Q_{1}} \right)^{2}} + {K_{1 - 2} \times Q_{1}^{2}} + {K_{1 - 3} \times \left( {Q_{1} + Q_{2}} \right)^{2}}}} & \left( {{Equation}\mspace{14mu} 5.2} \right)\end{matrix}$

In a similar manner, a second path to Station B is through theopening(s) 1334 of the fifth section 1318 (shown in FIGS. 31-34) of theretention portion 1330. A modified loss calculation for Path 2 iscalculated as follows:

$\begin{matrix}{K^{\prime} = {{{Inlet}\mspace{14mu}{Loss}} + {{Flow}\mspace{14mu}{Junction}\mspace{14mu}{Loss}}}} & \left( {{Equation}\mspace{14mu} 5.1} \right) \\{K_{B}^{\prime} = {{K_{2 - 1} \times \left( {\frac{A_{Pipe}}{A_{2}} \times Q_{2}} \right)^{2}} + {K_{2 - 2} \times \left( {Q_{1} + Q_{2}} \right)^{2}}}} & \left( {{Equation}\mspace{14mu} 5.2} \right)\end{matrix}$

The modified loss coefficients of both Path 1 and Path 2 must equate toensure the volumetric flow rates (Q₁ and Q₂) reflect the balanceddistribution within the manifold at Station B. The volumetric flow ratesare adjusted until equal modified loss coefficients for both paths isachieved. The volumetric flow rates can be adjusted because theyrepresent a fractional portion of a total volumetric flow rate(Q′_(Total)), which is assumed to be unity for the purpose of thisstep-by-step solution. Upon equating the two modified loss coefficients,one can then proceed to equating the two paths to reach station C (thefourth section 1316 in FIGS. 31-34).

Loss coefficients between Station B (flow through drainage lumen in thefifth section 1318) and Station C (flow through lumen in the fourthsection 1316) are calculated in a similar manner as shown by Equations5.1 and 5.2). For example, for Path 1 (Station B to Station C), themodified loss coefficient (K′) for the opening(s) of the fourth section1316 is defined as:

K′=Loss to Station B+Friction Loss+Flow Junction Loss  (Equation 6.1)

K′ _(C) =K′ _(B) +K ₂₋₃×(Q ₁ +Q ₂)² +K ₂₋₄×(Q ₁ +Q ₂ +Q ₃)²  (Equation6.2)

For Path 2 (Station B to C), the modified loss coefficient (K′) based onthe flow area of the opening(s) of the fourth section 1316 are definedas:

$\begin{matrix}{\mspace{79mu}{K^{\prime} = {{{Inlet}\mspace{14mu}{Loss}} + {{Flow}\mspace{14mu}{Junction}\mspace{14mu}{Loss}}}}} & \left( {{Equation}\mspace{14mu} 7.1} \right) \\{K_{C}^{\prime} = {{K_{3 - 1} \times \left( {\frac{A_{Pipe}}{A_{3}} \times Q_{3}} \right)^{2}} + {K_{3 - 2} \times \left( {Q_{1} + Q_{2} + Q_{3}} \right)^{2}}}} & \left( {{Equation}\mspace{14mu} 7.2} \right)\end{matrix}$

As with the previous stations, the modified loss coefficients of bothPath 1 and Path 2 must equate to ensure the volumetric flow rates (Q₁,Q₂, and Q₃) reflect the balanced distribution within the manifold up toStation C. Upon equating the two modified loss coefficients, one canthen proceed to equating the two paths to reach Station D, Station E,and Station F. The step-by-step solution process proceeds through eachstation as demonstrated until calculating the modified loss coefficientfor the final station, Station F in this case. The Total LossCoefficient (K) for the manifold can then be calculated using an actualQ_(Total) (volumetric flow rate through a proximal portion of thedrainage lumen) determined through experimental measurement.

$\begin{matrix}{K = \frac{K_{F}^{\prime}}{Q_{Total}}} & \left( {{Equation}\mspace{14mu} 8} \right)\end{matrix}$

The fractional volumetric flow rates calculated through the step-by-stepexercise can then be multiplied by the actual total volumetric flow rate(Q_(Total)) to determine the flow through each opening 1232 (shown inFIGS. 30A-3E) and open distal end 1220.

EXAMPLES

Examples are provided below and shown in Tables 3-5 and FIGS. 35A-35Cfor the calculated volumetric flow rates.

Example 1

Example 1 illustrates a distribution of fluid flow for a retentionmember tube with different sized openings, which corresponds to theembodiment of the retention member 1330 shown in FIG. 31. As shown inTable 3, the proximal most opening (Q₆) had a diameter of 0.48 mm, thedistal-most opening (Q₅) on the sidewall of the tube had a diameter of0.88 mm, and the open distal end (Q₆) of the tube had a diameter of 0.97mm. Each of the openings was circular.

The Percentage of Flow Distribution and Calculated Volumetric Flow Ratewere determined as follows.

Path to Station B through distal end of tube (Path 1) f 8.4 = C_(f)/Re(C_(f) = 64 for circular cross-section) K_(INLET) 0.16 (Contractioncoefficient. for sharp edged orifice entering pipe) K_(ORIFICE) 2.8(Contraction coefficient. for sharp edged orifice w/no outlet pipe)K_(FRICTION) = f*(L/D) (Dependent on the length between orifices) Part1-1 = Inlet loss coef × (A_(T)/A₁ × Q′₁)² Part 1-2 = Catheter frictionloss × Q′₁ ² Part 1-3 = Through flow junction loss to station 2 × (Q′₁ +Q′₂)² A₂/A_(T) = 0.82 Q′₂/(Q′₁ + Q′₂) = 0.83 K₁₋₃ = 0.61 (From Miller,see table above) Part1-1 = 0.0000 Part 1-2 = 0.0376 Part 1-3 = 0.0065 K′= 0.0442 Path to Station B through sidewall opening (Path 2) Part 2-1 =Orifice loss coef x (A_(T)/A₂ × Q′₂)² Part 2-2 = Branch flow junctionloss to station 2 × (Q′₁ + Q′₂)² A₂/A_(T) = 0.82 Q′₂/(Q′₁ + Q′₂) = 0.83K₂₋₂ = 1.3 (From Chart 13.10 of Miller) Part 2-1 = 0.0306 Part 2-2 =0.0138 K′ = 0.0444 Path to Station C from Station B (Path 1 + Path 2)Part 2-3 = Catheter friction loss × (Q′₁ + Q′₂)² Part 2-4 = Through flowjunction loss to station 3 × (Q′₁ + Q′₂ + Q′₃)² A₃/A_(T) = 0.61Q′₃/(Q′₁ + Q′₂ + Q′₃) = 0.76 K₂₋₄ = 0.71 (From Chart 13.11 of Miller)Loss coefficient to Station 2 = 0.044 Part 2-3 = 0.921 Part 2-4 = 0.130K′ = 1.095 Path to Station C through sidewall opening (Path 3) Part 3-1= Orifice loss coef × (A_(T)/A₃ × Q′₃)² Part 3-2 = Branch flow junctionloss to station 3 × (Q′₁ + Q′₂ + Q′₃)² A₃/A_(T) = 0.61 Q′₃/(Q′₁ + Q′₂ +Q′₃) = 0.76 K₃₋₂ = 1.7 (From Chart 13.10 of Miller) Part 3-1 = 0.785Part 3-2 = 0.311 K′ = 1.096 Path to Station D from Station C (Path 1 +Path 2 + Path 3) Part 3-3 = Catheter friction loss × (Q′₁ + Q′₂ + Q′₃)²Part 3-4 = Through flow junction loss to station 4 × (Q′₁ + Q′₂ + Q′₃ +Q′₄)² A₄/A_(T) = 0.46 Q′₄/(Q′₁ + Q′₂ + Q′₃ + Q′₄) = 0.70 K₃₋₄ = 0.77(From Chart 13.11 of Miller) Loss coefficient to Station 3 = 1.10 Part3-3 = 15.90 Part 3-4 = 1.62 K′ = 18.62 Path to Station D throughsidewall opening (Path 4) Part 4-1 = Orifice loss coef × (A_(T)/A₄ ×Q′₄)² Part 4-2 = Branch flow junction loss to station 4 × (Q′₁ + Q′₂ +Q′₃ + Q′₄)² A₄/A_(T) = 0.46 Q′₄/(Q′₁ + Q′₂ + Q′₃ + Q′₄) = 0.70 K₄₋₂ =2.4 (From Chart 13.10 of Miller) Part 4-1 = 13.59 Part 4-2 = 5.04 K′ =18.62 Path to Station E from Station D (Path 1 + Path 2 + Path 3 + Path4) Part 4-3 = Catheter friction loss × (Q′₁ + Q′₂ + Q′₃ + Q′₄)² Part 4-4= Through flow junction loss to station 5 × (Q′₁ + Q′₂ + Q′₃ + Q′₄ +Q′₅)² A₅/A_(T) = 0.36 Q′₅/(Q′₁ + Q′₂ + Q′₃ + Q′₄ + Q′₅) = 0.65 K₃₋₄ =0.78 (From Chart 13.11 of Miller) Loss coefficient to Station 4 = 18.6Part 4-3 = 182.3 Part 4-4 = 13.3 K′ = 214.2 Path to Station E throughsidewall opening (Path 5) Part 5-1 = Orifice loss coef × (A_(T)/A₅ ×Q′₅)² Part 5-2 = Branch flow junction loss to station 5 × (Q′₁ + Q′₂ +Q′₃ + Q′₄ + Q′₅)² A₅/A_(T) = 0.36 Q′₅/(Q′₁ + Q′₂ + Q′₃ + Q′₄ + Q′₅) =0.65 K₄₋₂ = 3.3 (From Chart 13.10 of Miller) Part 5-1 = 157.8 Part 5-2 =56.4 K′ = 214.2 Path to Station F from Station E (through paths 1-5)Part 5-3 = Catheter friction loss × (Q′₁ + Q′₂ + Q′₃ + Q′₄ + Q′₅)² Part5-4 = Through flow junction loss to station 6 × (Q′₁ + Q′₂ + Q′₃ + Q′₄ +Q′₅ + Q′₆)² A₆/A_(T) = 0.24 Q′₆/(Q′₁ + Q′₂ + Q′₃ + Q′₄ + Q′₅ + Q′₆) =0.56 K₃₋₄ = 0.77 (From Chart 13.11 of Miller) Loss coefficient toStation 5 = 214.2 Part 5-3 = 1482.9 Part 5-4 = 68.3 K′ = 1765.4 Path toStation F through sidewall opening (path 6) Part 6-1 = Orifice loss coef× (A_(T)/A₆ × Q′₆)² Part 6-2 = Branch flow junction loss to station 6 ×(Q′₁ + Q′₂ + Q′₃ + Q′₄ + Q′₅ + Q′₆)² A₆/A_(T) = 0.24 Q′₆/(Q′₁ + Q′₂ +Q′₃ + Q′₄ + Q′₅ + Q′₆) = 0.56 K₄₋₂ = 5.2 (From Chart 13.10 of Miller)Part 6-1 = 1304.3 Part 6-2 = 461.2 K′ = 1765.5

In order to calculate flow distribution for each “Station” or opening,the calculated K′ values were multiplied by actual total volumetric flowrate (Q_(Total)) to determine the flow through each perforation anddistal end hole. Alternatively, calculated results could be presented asa percentage of total flow or a flow distribution as shown in Table 3.As shown in Table 3 and in FIG. 35C, the Percentage of Flow Distribution(% Flow Distribution) through the proximal most opening (Q6) was 56.1%.Flow through the two proximal-most holes (Q6 and Q5) was 84.6%.

TABLE 3 % Flow Diameter Length Cumulative Position Distribution (mm)(mm) Length (mm) Q₆′ (proximal) 56.1% 0.48 0 0 Q₅′ 28.5% 0.58 10 10 Q₄′10.8% 0.66 10 20 Q₃′ 3.5% 0.76 10 30 Q₂′ 0.9% 0.88 10 40 Q₁′ (distal)0.2% 0.97 15 55 Q_(TOTAL) 100%

As demonstrated in Example 1, by increasing hole diameter andcross-sectional area from the proximal to distal regions of theretention portion, distribution of fluid flow was more evenlydistributed across the entire retention portion.

Example 2

In Example 2, each opening has the same diameter and area. As shown inTable 4 and FIG. 35A, flow distribution through the proximal-mostopening is 86.2% of total flow through the tube. Flow distributionthrough the second opening is 11.9%. Therefore, in this example, it wascalculated that 98.1% of fluid passing through the drainage lumenentered the lumen through the two proximal-most openings. Compared toExample 1, Example 2 has increased flow through the proximal end of thetube. Therefore, Example 1 provides a wider flow distribution in which agreater percentage of fluid enters the drainage lumen through openingsother than the proximal-most opening. As such, fluid can be moreefficiently collected through multiple openings reducing fluid backupand improving distribution of negative pressure through the renal pelvisand/or kidneys.

TABLE 4 % Flow Diameter Length Cumulative Position Distribution (mm)(mm) Length (mm) Q₆′ (proximal) 86.2% 0.88 0 0 Q₅′ 11.9% 0.88 22 22 Q₄′1.6% 0.88 22 44 Q₃′ 0.2% 0.88 22 66 Q₂′ 0.03% 0.88 22 88 Q₁′ (distal)0.01% 0.97 22 110 Q_(TOTAL) 100%

Example 3

Example 3 also illustrates flow distribution for openings having thesame diameter. However, as shown in Table 5, the openings are closertogether (10 mm vs. 22 mm). As shown in Table 5 and FIG. 35B, 80.9% offluid passing through the drainage lumen entered the drainage lumenthrough the proximal most opening (Q₆). 96.3% of fluid in the drainagelumen entered the drainage lumen through the two proximal-most openings(Q₅ and Q₆).

TABLE 5 % Flow Diameter Length Cumulative Position Distribution (mm)(mm) Length (mm) Q₆′ (proximal) 80.9% 0.88 0 0 Q₅′ 15.4% 0.88 10 10 Q₄′2.9% 0.88 10 20 Q₃′ 0.6% 0.88 10 30 Q₂′ 0.1% 0.88 10 40 Q₁′ (distal)0.02% 0.97 15 55 Q_(TOTAL) 100%

Additional Exemplary Ureteral Catheters

As shown in FIG. 1, a urine collection assembly 100 including ureteralcatheters 112, 114 configured to be positioned within the urinary tractof a patient is illustrated. For example, distal ends 120, 121 of theureteral catheters 112, 114 can be configured to be deployed in thepatient's ureters 2, 4 and, in particular, in a renal pelvis 20, 21 areaof the kidneys 6, 8.

In some examples, the urine collection assembly 100 can comprise twoseparate ureteral catheters, such as a first catheter 112 disposed in oradjacent to the renal pelvis 20 of the right kidney 2 and a secondcatheter 114 disposed in or adjacent to the renal pelvis 21 of the leftkidney 4. The catheters 112, 114 can be separate for their entirelengths, or can be held in proximity to one another by a clip, ring,clamp, or other type of connection mechanism (e.g., connector 150) tofacilitate placement or removal of the catheters 112, 114. In someexamples, catheters 112, 114 can merge or be connected together to forma single drainage lumen. In other examples, the catheters 112, 114 canbe inserted through or enclosed within another catheter, tube, or sheathalong portions or segments thereof to facilitate insertion andretraction of the catheters 112, 114 from the body. For example, abladder catheter 116 can be inserted over and/or along the sameguidewire as the ureteral catheters 112, 114, thereby causing theureteral catheters 112, 114 to extend from the distal end of the bladdercatheter 116.

With reference to FIGS. 1, 2A, and 2B, an exemplary ureteral catheter112 can comprise at least one elongated body or tube 122, the interiorof which defines or comprises one or more drainage channel(s) orlumen(s), such as drainage lumen 124. The tube 122 size can range fromabout 1 Fr to about 9 Fr (French catheter scale). In some examples, thetube 122 can have an external diameter ranging from about 0.33 to about3 mm, and an internal diameter ranging from about 0.165 to about 2.39mm. In one example, the tube 122 is 6 Fr and has an outer diameter of2.0±0.1 mm. The length of the tube 122 can range from about 30 cm toabout 120 cm depending on the age (e.g., pediatric or adult) and genderof the patient.

The tube 122 can be formed from a flexible and/or deformable material tofacilitate advancing and/or positioning the tube 122 in the bladder 10and ureters 6, 8 (shown in FIG. 1). The catheter material should beflexible and soft enough to avoid or reduce irritation of the renalpelvis and ureter, but should be rigid enough that the tube 122 does notcollapse when the renal pelvis or other portions of the urinary tractexert pressure on the exterior of the tube 122, or when the renal pelvisand/or ureter are drawn against the tube 122 during inducement ofnegative pressure. For example, the tube 122 can be formed frommaterials including biocompatible polymers, polyvinyl chloride,polytetrafluoroethylene (PTFE) such as Teflon®, silicone coated latex,or silicone. In one example, the tube 122 is formed from a thermoplasticpolyurethane. At least a portion or all of the catheter 112, such as thetube 122, can be coated with a hydrophilic coating to facilitateinsertion and/or removal, and/or to enhance comfort. In some examples,the coating is a hydrophobic and/or lubricious coating. For example,suitable coatings can comprise ComfortCoat® hydrophilic coating which isavailable from Koninklijke DSM N.V. or hydrophilic coatings comprisingpolyelectrolyte(s) such as are disclosed in U.S. Pat. No. 8,512,795,which is incorporated herein by reference.

In some examples, the tube 122 can comprise: a distal portion 118 (e.g.,a portion of the tube 122 configured to be positioned in the ureter 6, 8and renal pelvis 20, 21); a middle portion 126 (e.g., a portion of thetube 122 configured to extend from the distal portion through theureteral openings 16 into the patient's bladder 10 and urethra 12); anda proximal portion 128 (e.g., a portion of the tube 122 extending fromthe urethra 12 to an external fluid collection container and/or pumpassembly). In one preferred example, the combined length of the proximalportion 128 and the middle portion 126 of the tube 122 is about 54±2 cm.In some examples, the tube 122 terminates in another indwelling catheterand/or drainage lumen, such as in a drainage lumen of the bladdercatheter 116. In that case, fluid drains from the proximal end of theureteral catheter 112, 114 and is directed from the body through theadditional indwelling catheter and/or drainage lumen.

Additional Exemplary Ureteral Retention Portions:

With continued reference to FIGS. 1, 2A, and 2B, the distal portion 118of the ureteral catheter 112 comprises a retention portion 130 formaintaining the distal end 120 of the catheter 112 at a desired fluidcollection position proximate to or within the renal pelvis 20, 21 ofthe kidney 2, 4. In some examples, the retention portion 130 isconfigured to be flexible and bendable to permit positioning of theretention portion 130 in the ureter and/or renal pelvis. The retentionportion 130 is desirably sufficiently bendable to absorb forces exertedon the catheter 112 and to prevent such forces from being translated tothe ureters. For example, if the retention portion 130 is pulled in theproximal direction P (shown in FIG. 3A) toward the patient's bladder,the retention portion 130 can be sufficiently flexible to begin tounwind or be straightened so that it can be drawn through the ureter.Similarly, when the retention portion 130 can be reinserted into therenal pelvis or other suitable region within the ureter, it can bebiased to return to its deployed configuration.

In some examples, the retention portion 130 is integral with the tube122. In that case, the retention portion 130 can be formed by impartinga bend or curl to the catheter body 122 that is sized and shaped toretain the catheter at a desired fluid collection location. Suitablebends or coils can include a pigtail coil, corkscrew coil, and/orhelical coil. For example, the retention portion 130 can comprise one ormore radially and longitudinally extending helical coils configured tocontact and passively retain the catheter 112 within the ureter 6, 8proximate to or within the renal pelvis 20, 21. In other examples, theretention portion 130 is formed from a radially flared or taperedportion of the catheter body 122. For example, the retention portion 130can further comprise a fluid collecting portion, as shown in FIGS. 4Aand 4B, such as a tapered or funnel-shaped inner surface 186. In otherexamples, the retention portion 130 can comprise a separate elementconnected to and extending from the catheter body or tube 122.

The retention portion 130 can further comprise one or more perforatedsections, such as drainage holes or ports 132 (shown in FIGS. 3A-3E). Adrainage port can be located, for example, at the open distal end 120,121 of the tube 122. In other examples, perforated sections and/ordrainage ports 132 are disposed along the sidewall of the distal portion118 of the catheter tube 122. The drainage ports or holes can be usedfor assisting in fluid collection. In other examples, the retentionportion 130 is solely a retention structure and fluid collection and/orimparting negative pressure is provided by structures at other locationson the catheter tube 122.

Referring now to FIGS. 2A, 2B, and 3A-3E, exemplary retention portions130 comprising a plurality of helical coils, such as one or more fullcoils 184 and one or more half or partial coils 183, are illustrated.The retention portion 130 is capable of moving between a contractedposition and the deployed position with the plurality of helical coils.For example, a substantially straight guidewire can be inserted throughthe retention portion 130 to maintain the retention portion 130 in asubstantially straight contracted position. When the guidewire isremoved, the retention portion 130 can transition to its coiledconfiguration. In some examples, the coils 183, 184 extend radially andlongitudinally from the distal portion 118 of the tube 122. Withspecific reference to FIGS. 2A and 2B, in a preferred exemplaryembodiment, the retention portion 130 comprises two full coils 184 andone half coil 183. The outer diameter of the full coils 184, shown byline D1, can be about 18±2 mm. The half coil 183 diameter D2 can beabout 14 mm. The coiled retention portion 130 has a height H of about16±2 mm. The retention portion 130 can further comprise the one or moredrainage holes 132 (shown in FIGS. 3A-3E) configured to draw fluid intoan interior of the catheter tube 122. In some examples, the retentionportion 130 can comprise six drainage holes, plus an additional hole atthe distal tip 120 of the retention portion. The diameter of each of thedrainage holes 132 (shown in FIGS. 3A-3E) can range from about 0.7 mm to0.9 mm and, preferably, is about 0.83±0.01 mm. The distance betweenadjacent drainage holes 132, specifically the linear distance betweendrainage holes 132 when the coils are straightened, can be about22.5±2.5 mm.

As shown in FIGS. 3A-3E, in another exemplary embodiment, the distalportion 118 of the drainage lumen proximal to the retention portion 130defines a straight or curvilinear central axis L. In some examples, atleast a half or first coil 183 and a full or second coil 184 of theretention portion 130 extend about an axis A of the retention portion130. The first coil 183 initiates or begins at a point where the tube122 is bent at an angle α ranging from about 15 degrees to about 75degrees from the central axis L, as indicated by angle α, and preferablyabout 45 degrees. As shown in FIGS. 3A and 3B, prior to insertion in thebody, the axis A can be coextensive with the longitudinal central axisL. In other examples, as shown in FIGS. 3C-3E, prior to insertion in thebody, the axis A extends from and is curved or angled, for example atangle (3, relative to the central longitudinal axis L.

In some examples, multiple coils 184 can have the same inner and/orouter diameter D and height H2. In that case, the outer diameter D1 ofthe coils 184 may range between 10 mm and 30 mm. The height H2 betweencoils 184 may be about 3 mm to 10 mm.

In other examples, the retention portion 130 is configured to beinserted in the tapered portion of the renal pelvis. For example, theouter diameter D1 of the coils 184 can increase toward the distal end120 of the tube 122, resulting in a helical structure having a taperedor partially tapered configuration. For example, the distal or maximumouter diameter D1 of the tapered helical portion ranges from about 10 mmto about 30 mm, which corresponds to the dimensions of the renal pelvis.The height H2 of the retention portion 130 ranges from about 10 mm toabout 30 mm.

In some examples, the outer diameter D1 and/or height H2 of the coils184 can vary in a regular or irregular fashion. For example, the outerdiameter D1 of coils or height H2 between coils can increase or decreaseby a regular amount (e.g., about 10% to about 25% between adjacent coils184). For example, for a retention portion 130 having three coils (asshown, for example, in FIGS. 3A and 3B) an outer diameter D3 of aproximal-most coil or first coil 183 can be about 6 mm to 18 mm, anouter diameter D2 of a middle coil or second coil 185 can be about 8 mmto about 24 mm, and an outer diameter D1 of a distal-most or third coil187 can be between about 10 mm and about 30 mm.

The retention portion 130 can further comprise the drainage ports 132 orholes disposed on or through the sidewall of the catheter tube 122 on oradjacent to the retention portion 130 to permit urine waste to flow fromthe outside of the catheter tube 122 to the inside of the catheter tube122. The position and size of the drainage ports 132 can vary dependingupon the desired flow rate and configuration of the retention portion.The diameter of the drainage ports 132 can range from about 0.005 mm toabout 1.0 mm. The spacing between the drainage ports 132 can range fromabout 0.1 mm to about 255 mm. The drainage ports 132 can be spaced inany arrangement, for example, linear or offset. In some examples, thedrainage ports 132 can be non-circular, and can have a surface area ofabout 0.002 mm² to 0.79 mm² or more.

In some examples, as shown in FIG. 3A, the drainage ports 132 arelocated around the entire periphery of the sidewall of the catheter tube122 to increase an amount of fluid that can be drawn into the drainagelumen 124 (shown in FIGS. 1, 2A, and 2B). In other examples, as shown inFIGS. 3B-3E, the drainage ports 132 can be disposed essentially only oronly on the radially inwardly facing side of the coils 184 to preventocclusion or blockage of the drainage ports 132, and the outwardlyfacing side of the coils may be essentially free of drainage ports 132or free of drainage ports 132. For example, when negative pressure isinduced in the ureter and/or renal pelvis, mucosal tissue of the ureterand/or kidney may be drawn against the retention portion 130 and mayocclude some drainage ports 132 on the outer periphery of the retentionportion 130. Drainage ports 132 located on the radially inward side ofthe retention structure would not be appreciably occluded when suchtissues contact the outer periphery of the retention portion 130.Further, risk of injury to the tissues from pinching or contact with thedrainage ports 132 can be reduced or ameliorated.

With reference to FIGS. 3C and 3D, other examples of ureteral catheters112 having a retention portion 130 comprising a plurality of coils areillustrated. As shown in FIG. 3C, the retention portion 130 comprisesthree coils 184 extending about the axis A. The axis A is a curved arcextending from the central longitudinal axis L of the portion of thedrainage lumen 181 proximal to the retention portion 130. The curvatureimparted to the retention portion 130 can be selected to correspond tothe curvature of the renal pelvis, which comprises a cornucopia-shapedcavity.

As shown in FIG. 3D, in another exemplary embodiment, the retentionportion 130 can comprise two coils 184 extending about an angled axis A.The angled axis A extends at an angle from a central longitudinal axisL, and is angled, as shown by angle (3, relative to an axis generallyperpendicular to the central axis L of the portion of the drainagelumen. The angle (3 can range from about 15 to about 75 degrees (e.g.,about 105 to about 165 degrees relative to the central longitudinal axisL of the drainage lumen portion of the catheter 112).

FIG. 3E shows another example of a ureteral catheter 112. The retentionportion comprises three helical coils 184 extending about an axis A. Theaxis A is angled, as shown by angle β, relative to the horizontal. As inthe previously-described examples, the angle β can range from about 15to about 75 degrees (e.g., about 105 to about 165 degrees relative tothe central longitudinal axis L of the drainage lumen portion of thecatheter 112).

With reference to FIGS. 4A and 4B, in another example, a retentionportion 130 of a ureteral catheter 112 comprises a catheter tube 122having a widened and/or tapered distal end portion which, in someexamples, is configured to be positioned in the patient's renal pelvisand/or kidney. For example, the retention portion 130 can be afunnel-shaped structure comprising an outer surface 185 configured to bepositioned against the ureter and/or kidney wall and comprising an innersurface 186 configured to direct fluid toward a drainage lumen 124 ofthe catheter 112. The retention portion 130 can comprise a proximal end188 adjacent to the distal end of the drainage lumen 124 and having afirst diameter D1 and a distal end 190 having a second diameter D2 thatis greater than the first diameter D1 when the retention portion 130 isin its deployed position. In some examples, the retention portion 130 istransitionable from a collapsed or compressed position to the deployedposition. For example, the retention portion 130 can be biased radiallyoutward such that when the retention portion 130 is advanced to itsfluid collecting position, the retention portion 130 (e.g., the funnelportion) expands radially outward to the deployed state.

The retention portion 130 of the ureteral catheter 112 can be made froma variety of suitable materials that are capable of transitioning fromthe collapsed state to the deployed state. In one example, the retentionportion 130 comprises a framework of tines or elongated members formedfrom a temperature sensitive shape memory material, such as nitinol. Insome examples, the nitinol frame can be covered with a suitablewaterproof material such as silicone to form a tapered portion orfunnel. In that case, fluid is permitted to flow down the inner surface186 of the retention portion 130 and into the drainage lumen 124. Inother examples, the retention portion 130 is formed from various rigidor partially rigid sheets or materials bended or molded to form afunnel-shaped retention portion as illustrated in FIGS. 4A and 4B.

In some examples, the retention portion of the ureteral catheter 112 caninclude one or more mechanical stimulation devices 191 for providingstimulation to nerves and muscle fibers in adjacent tissues of theureter(s) and renal pelvis. For example, the mechanical stimulationdevices 191 can include linear or annular actuators embedded in ormounted adjacent to portions of the sidewall of the catheter tube 122and configured to emit low levels of vibration. In some examples,mechanical stimulation can be provided to portions of the ureters and/orrenal pelvis to supplement or modify therapeutic effects obtained byapplication of negative pressure. While not intending to be bound bytheory, it is believed that such stimulation affects adjacent tissuesby, for example, stimulating nerves and/or actuating peristaltic musclesassociated with the ureter(s) and/or renal pelvis. Stimulation of nervesand activation of muscles may produce changes in pressure gradients orpressure levels in surrounding tissues and organs which may contributeto or, in some cases, enhance therapeutic benefits of negative pressuretherapy.

With reference to FIGS. 5A and 5B, according to another example, aretention portion 330 of a ureteral catheter 312 comprises a cathetertube 322 having a distal portion 318 formed in a helical structure 332and an inflatable element or balloon 350 positioned proximal to thehelical structure 332 to provide an additional degree of retention inthe renal pelvis and/or fluid collection location. A balloon 350 can beinflated to pressure sufficient to retain the balloon in the renalpelvis or ureter, but low enough to avoid distending or damaging thesestructures. Suitable inflation pressures are known to those skilled inthe art and are readily discernible by trial and error. As inpreviously-described examples, the helical structure 332 can be impartedby bending the catheter tube 322 to form one or more coils 334. Thecoils 334 can have a constant or variable diameter and height asdescribed above. The catheter tube 322 further comprises a plurality ofdrainage ports 336 disposed on the sidewall of the catheter tube 322 toallow urine to be drawn into the drainage lumen 324 of the catheter tube322 and to be directed from the body through the drainage lumen 324, forexample on the inwardly facing and/or outwardly facing sides of the coil334.

As shown in FIG. 5B, the inflatable element or balloon 350 can comprisean annular balloon-like structure having, for example, a generallyheart-shaped cross section and comprising a surface or cover 352defining a cavity 353. The cavity 353 is in fluid communication with aninflation lumen 354 extending parallel to the drainage lumen 324 definedby the catheter tube 322. The balloon 350 can be configured to beinserted in the tapered portion of the renal pelvis and inflated suchthat an outer surface 356 thereof contacts and rests against an innersurface of the ureter and/or renal pelvis. The inflatable element orballoon 350 can comprise a tapered inner surface 358 extendinglongitudinally and radially inward toward the catheter tube 322. Theinner surface 358 can be configured to direct urine toward the cathetertube 322 to be drawn into the drainage lumen 324. The inner surface 358can also be positioned to prevent fluid from pooling in the ureter, suchas around the periphery of the inflatable element or balloon 350. Theinflatable retention portion or balloon 350 is desirably sized to fitwithin the renal pelvis and can have a diameter ranging from about 10 mmto about 30 mm.

With reference to FIGS. 6 and 7, in some examples, an assembly 400including a ureteral catheter 412 comprising a retention portion 410 isillustrated. The retention portion 410 is formed from a porous and/orsponge-like material that is attached to a distal end 421 of a cathetertube 422. The porous material can be configured to channel and/or absorburine and direct the urine toward a drainage lumen 424 of the cathetertube 422. As shown in FIG. 7, the retention portion 410 can be a porouswedge shaped-structure configured for insertion and retention in thepatient's renal pelvis. The porous material comprises a plurality ofholes and/or channels. Fluid can be drawn through the channels andholes, for example, by gravity or upon inducement of negative pressurethrough the catheter 412. For example, fluid can enter the wedge-shapedretention portion 410 through the holes and/or channels and is drawntoward a distal opening 420 of the drainage lumen 424, for example, bycapillary action, peristalsis, or as a result of the inducement ofnegative pressure in the holes and/or channels. In other examples, asshown in FIG. 7, the retention portion 410 comprises a hollow, funnelstructure formed from the porous sponge-like material. As shown by arrowA, fluid is directed down an inner surface 426 of the funnel structureinto the drainage lumen 424 defined by the catheter tube 422. Also,fluid can enter the funnel structure of the retention portion 410through holes and channels in the porous sponge-like material of asidewall 428. For example, suitable porous materials can includeopen-celled polyurethane foams, such as polyurethane ether. Suitableporous materials can also include laminates of woven or non-woven layerscomprising, for example, polyurethane, silicone, polyvinyl alcohol,cotton, or polyester, with or without antimicrobial additives such assilver, and with or without additives for modifying material propertiessuch as hydrogels, hydrocolloids, acrylic, or silicone.

With reference to FIG. 8, according to another example, a retentionportion 500 of a ureteral catheter 512 comprises an expandable cage 530.The expandable cage 530 comprises one or more longitudinally andradially extending hollow tubes 522. For example, the tubes 522 can beformed from an elastic, shape memory material such as nitinol. The cage530 is configured to transition from a contracted state, for insertionthrough the patient's urinary tract, to a deployed state for positioningin the patient's ureters and/or kidney. The hollow tubes 522 comprise aplurality of drainage ports 534 which can be positioned on the tubes,for example, on radially inward facing sides thereof. The ports 534 areconfigured to permit fluid to flow or be drawn through the ports 534 andinto the respective tubes 522. The fluid drains through the hollow tubes522 into a drainage lumen 524 defined by a catheter body 526 of theureteral catheter 512. For example, fluid can flow along the pathindicated by the arrows 532 in FIG. 8. In some examples, when negativepressure is induced in the renal pelvis, kidneys, and/or ureters,portions of the ureter wall and/or renal pelvis may be drawn against theoutward facing surfaces of the hollow tubes 522. The drainage ports 534are positioned and configured so as not to be appreciably occluded byureteral structures upon application of negative pressure to the uretersand/or kidney.

Exemplary Urine Collection Assemblies:

Referring now to FIGS. 1, 9A, and 11A, the urine collection assembly 100further comprises a bladder catheter 116. The distal ends 120, 121 ofthe ureteral catheters 112, 114 can be connected to the bladder catheter116 to provide a single drainage lumen for urine, or the ureteralcatheter(s) can drain via separate tube(s) from the bladder catheter116.

Exemplary Bladder Catheter

The bladder catheter 116 comprises a deployable seal and/or anchor 136for anchoring, retaining, and/or providing passive fixation forindwelling portions of the urine collection assembly 100 and, in someexamples, to prevent premature and/or untended removal of assemblycomponents during use. The anchor 136 is configured to be locatedadjacent to the lower wall of the patient's bladder 10 (shown in FIG. 1)to prevent patient motion and/or forces applied to indwelling catheters112, 114, 116 from translating to the ureters. The bladder catheter 116comprises an interior of which defines a drainage lumen 140 configuredto conduct urine from the bladder 10 to an external urine collectioncontainer 712 (shown in FIG. 19). In some examples, the bladder catheter116 size can range from about 8 Fr to about 24 Fr. In some examples, thebladder catheter 116 can have an external diameter ranging from about2.7 to about 8 mm. In some examples, the bladder catheter 116 can havean internal diameter ranging from about 2.16 to about 6.2 mm. Thebladder catheter 116 can be available in different lengths toaccommodate anatomical differences for gender and/or patient size. Forexample, the average female urethra length is only a few inches, so thelength of a tube 138 can be rather short. The average urethra length formales is longer due to the penis and can be variable. It is possiblethat woman can use bladder catheters 116 with longer length tubes 138provided that the excess tubing does not increase difficulty inmanipulating and/or preventing contamination of sterile portions of thecatheter 116. In some examples, a sterile and indwelling portion of thebladder catheter 116 can range from about 1 inch to 3 inches (for women)to about 20 inches for men. The total length of the bladder catheter 116including sterile and non-sterile portions can be from one to severalfeet.

The catheter tube 138 can comprise one or more drainage ports 142configured to be positioned in the bladder 10 for drawing urine into thedrainage lumen 140. For example, excess urine left in the patient'sbladder 10 during placement of the ureteral catheters 112, 114 isexpelled from the bladder 10 through the ports 142 and drainage lumen140. In addition, any urine that is not collected by the ureteralcatheters 112, 114 accumulates in the bladder 10, and can be conductedfrom the urinary tract through the drainage lumen 140. The drainagelumen 140 may be pressurized to a negative pressure to assist in fluidcollection or may be maintained at atmospheric pressure such that fluidis collected by gravity and/or as a result of partial contraction of thebladder 10. In some examples, the ureteral catheters 112, 114 may extendfrom the drainage lumen 140 of the bladder catheter 116 to facilitateand/or simplify insertion and placement of the ureteral catheters 112,114.

With specific reference to FIG. 1, the deployable seal and/or anchor 136is disposed at or adjacent to a distal end 148 of the bladder catheter116. The deployable anchor 136 is configured to transition between acontracted state for insertion into the bladder 10 through the urethra12 and urethral opening 18 and a deployed state. The anchor 136 isconfigured to be deployed in and seated adjacent to a lower portion ofthe bladder 10 and/or against the urethral opening 18. For example, theanchor 136 can be positioned adjacent to the urethral opening 18 toenhance suction of a negative pressure applied to the bladder 10 or, inthe absence of negative pressure, to partially, substantially, orentirely seal the bladder 10 to ensure that urine in the bladder 10 isdirected through the drainage lumen 140 and to prevent leakage to theurethra 12. For a bladder catheter 116 including an 8 Fr to 24 Frelongated tube 138, the anchor 136 can be about 12 Fr to 32 Fr (e.g.,having a diameter of about 4 mm to about 10.7 mm) in the deployed state,and preferably between about 24 Fr and 30 Fr. A 24 Fr anchor has adiameter of about 8 mm. It is believed that a 24 Fr anchor 136 would bea single size suitable for all or most patients. For a catheter 116 witha 24 Fr anchor 136, a suitable length of the anchor 136 is between about1.0 cm and 2.3 cm, and preferably about 1.9 cm (about 0.75 in).

Exemplary Bladder Anchor Structures

With specific reference to FIGS. 1, 12A, and 13, an exemplary bladderanchor 136 in the form of an expandable balloon 144 is illustrated. Theexpandable (e.g., inflatable) balloon 144 can be, for example, aspherical balloon of a Foley catheter. The balloon 144 can be about 1.0cm to 2.3 cm in diameter, and preferably about 1.9 cm (0.75 in) indiameter. The balloon 144 is preferably formed from a flexible materialincluding, for example, biocompatible polymers, polyvinyl chloride,polytetrafluoroethylene (PTFE) such as Teflon®, silicone coated latex,or silicone.

The balloon 144 is in fluid connection with an inflation lumen 146, andis inflated by introducing fluid into the balloon 144. In a deployedstate, the balloon 144 can be a substantially spherical structuremounted to and extending radially outward from the catheter tube 138 ofthe bladder catheter 116 and comprising a central cavity or channel forthe catheter tube 138 to pass through. In some examples, the cathetertube 138 extends through the cavity defined by the balloon 144, suchthat the open distal end 148 of the catheter tube 138 extends distallybeyond the balloon 144 and toward the center of the bladder 10 (shown inFIG. 1). Excess urine collected in the bladder 10 can be drawn into thedrainage lumen 140 through the distal open end 148 thereof.

As shown in FIGS. 1 and 12A, in one example, the ureteral catheters 112,114 extend from the open distal end 148 of the drainage lumen 140. Inanother example, as shown in FIG. 14, the ureteral catheters 112, 114extend through ports 172 or openings disposed on a sidewall of thecatheter tube 138 at a position distal to the balloon 144. The ports 172can be circular or oval shaped. The ports 172 are sized to receive theureteral catheters 112, 114 and, accordingly, can have a diameterranging from about 0.33 mm to about 3 mm. As shown in FIG. 13, inanother example, the bladder catheter 116 is positioned next to theballoon 144, rather than extending through a central cavity defined bythe balloon 144. As in other examples, the ureteral catheters 112, 114extend through ports 172 in the sidewall of the bladder catheter 116 andinto the bladder 10.

With reference to FIG. 12B, a cross-sectional view of the bladdercatheter 116 and ureteral catheter(s) 112, 114 is shown. As shown inFIG. 12B, in one example, the bladder catheter 116 comprises a duallumen catheter with the drainage lumen 140 at a central region thereofand a smaller inflation lumen 146 extending along the periphery of thecatheter tube 138. The ureteral catheters 112, 114 are inserted orenclosed in the central drainage lumen 140. The ureteral catheters 112,114 are single-lumen catheters having a sufficiently narrow crosssection to fit within the drainage lumen 140. In some examples, asdiscussed above, the ureteral catheters 112, 114 extend through theentire bladder catheter 116. In other examples, the ureteral catheters112, 114 terminate in the drainage lumen 140 of the bladder catheter116, either at a position in the patient's ureter 12 or in an externalportion of the drainage lumen 140. As shown in FIG. 12C, in anotherexample, a bladder catheter 116 a is a multi-lumen catheter that definesat least four lumens, namely a first lumen 112 a for conducting fluidfrom the first ureteral catheter 112 (shown in FIG. 1), a second lumen114 a for conducting fluid from the second ureteral catheter 114 (shownin FIG. 1), a third lumen 140 a for drainage of urine from the bladder10 (shown in FIG. 1), and the inflation lumen 146 a for conducting fluidto and from the balloon 144 (shown in FIG. 12A) for inflation andretraction thereof.

As shown in FIG. 15, another example of a catheter balloon 144 for usewith a urine collection assembly 100 is illustrated. In the example ofFIG. 15, the balloon 144 is configured to be positioned partially withinthe patient's bladder 10 and partially within the urethra 12 to providean enhanced bladder seal. A central portion 145 of the balloon 144 isconfigured to be radially contracted by the urethral opening 18, therebydefining a bulbous upper volume configured to be positioned in the lowerportion of the bladder 10 and a bulbous lower volume configured to beposition at the distal portion of the urethra 12. As inpreviously-described examples, the bladder catheter 116 extends througha central cavity defined by the balloon 144 and toward a central portionof the bladder 10 and includes drainage ports 142 for conducting urinefrom the bladder 10 through a drainage lumen 140 of the catheter 116.The drainage ports 142 can be generally circular or oval shaped and canhave a diameter of about 0.005 mm to about 8.0 mm.

With reference again to FIGS. 9A and 9B, another example of a urinecollection assembly 100 including a bladder anchor device 134 isillustrated. The bladder anchor device 134 comprises a bladder catheter116 defining a drainage lumen 140, an inflation lumen 146, and an anchor136, namely, another example of an expandable balloon 144, configured tobe seated in a lower portion of the bladder 10. Unlike in thepreviously-described examples, the ports 142 configured to receive theureteral catheters 112, 114 are disposed proximal to and/or below theballoon 144. The ureteral catheters 112, 114 extend from the ports 142and, as in previously-described examples, extend through the ureteralorifices or openings of the bladder and into the ureters. When theanchor 136 is deployed in the bladder, the ports 142 are disposed in alower portion of the bladder adjacent to the urethral opening. Theureteral catheters 112, 114 extend from the ports 172 and between alower portion of the balloon 144 and the bladder wall. In some examples,the catheters 112, 114 may be positioned to prevent the balloon 144and/or bladder wall from occluding the ports 142 so that excess urinecollected in the bladder can be drawn into the ports 142 to be removedfrom the body.

With reference again to FIGS. 10A and 10B, in another example of a urinecollection assembly 200, an expandable cage 210 anchors the assembly 200in the bladder. The expandable cage 210 comprises a plurality offlexible members 212 or tines extending longitudinally and radiallyoutward from a catheter body 238 of a bladder catheter 216 which, insome examples, can be similar to those discussed above with respect tothe retention portion of the ureteral catheter of FIG. 8. The members212 can be formed from a suitable elastic and shape memory material suchas nitinol. In a deployed position, the members 212 or tines areimparted with a sufficient curvature to define a spherical or ellipsoidcentral cavity 242. The cage 210 is attached to an open distal open end248 of the catheter tube or body 238, to allow access to a drainagelumen 240 defined by the tube or body 238. The cage 210 is sized forpositioning within the lower portion of the bladder and can define adiameter and length ranging from 1.0 cm to 2.3 cm, and preferably about1.9 cm (0.75 in).

In some examples, the cage 210 further comprises a shield or cover 214over distal portions of the cage 210 to prevent or reduce the likelihoodthat tissue, namely, the distal wall of the bladder, will be caught orpinched as a result of contact with the cage 210 or member 212. Morespecifically, as the bladder contracts, the inner distal wall of thebladder comes into contact with the distal side of the cage 210. Thecover 214 prevents the tissue from being pinched or caught, may reducepatient discomfort, and protect the device during use. The cover 214 canbe formed at least in part from a porous and/or permeable biocompatiblematerial, such as a woven polymer mesh. In some examples, the cover 214encloses all or substantially all of the cavity 242. In that case, thecover 214 defines openings suitable for receiving the ureteral catheters112, 114. In some examples, the cover 214 covers only about the distal⅔, about the distal half, or about the distal third portion or anyamount, of the cage 210. In that case, the ureteral catheters 112, 114pass through the uncovered portion of the cage 210.

The cage 210 and cover 214 are transitionable from a contractedposition, in which the members 212 are contracted tightly togetheraround a central portion and/or around the bladder catheter 116 topermit insertion through a catheter or sheath to the deployed position.For example, in the case of a cage 210 constructed from a shape memorymaterial, the cage 210 can be configured to transition to the deployedposition when it is warmed to a sufficient temperature, such as bodytemperature (e.g., 37° C.). In the deployed position, the cage 210 has adiameter D that is preferably wider than the urethral opening, such thatthe cage 210 provides support for the ureteral catheters 112, 114 andprevents patient motion from translating through the ureteral catheters112, 114 to the ureters. When the assembly 200 is deployed in theurinary tract, the ureteral catheter(s) 112, 114 extend from the opendistal end 248 of the bladder catheter 216, past the longitudinallyextending members 212 of the cage 210, and into the bladder.Advantageously, the open (e.g., low profile) arrangement of the members212 or tines facilitates manipulation of the ureteral catheters 112, 114from the bladder catheter 116 and through the bladder. Particularly, theopen arrangement of the members 212 or tines does not obstruct orocclude the distal opening 248 and/or drainage ports of the bladdercatheter 216, making manipulation of the catheters 112, 114 easier toperform.

With reference to FIG. 16, a portion of another example of a urinecollection assembly 100 b is illustrated. The urine collection assembly100 b comprises a first ureteral catheter 112 b and a second ureteralcatheter 114 b. The assembly 100 b does not comprise a separate bladderdrainage catheter as is provided in the previously-described examples.Instead, one of the ureteral catheters 112 b comprises a helical portion127 b formed in the middle portion of the catheter 112 b (e.g., theportion of the catheter configured to be positioned in a lower portionof the patient's bladder). The helical portion 127 b comprises at leastone and preferably two or more coils 176 b. The coils 176 b can beformed by bending a catheter tube 138 b to impart a desired coilconfiguration. A lower coil 178 b of the helical portion 127 b isconfigured to be seated against and/or adjacent to the urethral opening.Desirably, the helical portion 127 b has a diameter D that is largerthan the urethral opening to prevent the helical portion 127 b frombeing drawn into the urethra. In some examples, a port 142 b or openingis disposed in the sidewall of the catheter tube 138 b for connectingthe first ureteral catheter 112 b to the second ureteral catheter 114 b.For example, the second catheter 114 b can be inserted in the port 142 bto form a fluid connection between the first ureteral catheter 112 b andthe second ureteral catheter 114 b. In some examples, the secondcatheter 114 b terminates at a position just inside a drainage lumen 140b of the first catheter 112 b. In other examples, the second ureteralcatheter 114 b is threaded through and/or extends along the length ofthe drainage lumen 140 b of the first catheter 112 b, but is not influid communication with the drainage lumen 140 b.

With reference again to FIGS. 11A and 11B, another exemplary urinecollection assembly 100 comprising a bladder anchor device 134 isillustrated. The assembly 100 includes ureteral catheters 112, 114 and aseparate bladder catheter 116. More specifically, as inpreviously-described examples, the assembly 100 includes the ureteralcatheters 112, 114, each of which comprise a distal portion 118positioned in or adjacent to the right kidney and the left kidney,respectively. The ureteral catheters 112, 114 comprise indwellingportions 118, 126, 128 extending through the ureters, bladder, andurethra. The ureteral catheters 112, 114 further comprise an externalportion 170 extending from the patient's urethra 12 to a pump assemblyfor imparting negative pressure to the renal pelvis and/or kidneys. Theassembly 100 also includes a bladder anchor device 134 comprising abladder catheter 116 and an anchor 136 (e.g., a Foley catheter) deployedin the bladder to prevent or reduce effects of patient motion from beingtranslated to the ureteral catheters 112, 114 and/or ureters. Thebladder catheter 116 extends from the bladder 10, through the urethra,and to a fluid collection container for fluid collection by gravity ornegative pressure drainage. In some examples, an external portion of thetubing extending between a collection vessel 712 and a pump 710 (shownin FIG. 19) can comprise one or more filters for preventing urine and/orparticulates from entering the pump. As in previously-describedexamples, the bladder catheter 116 is provided to drain excess urineleft in the patient's bladder during catheter placement.

Exemplary Connectors and Clamps:

With reference to FIGS. 1, 11A, and 17A-17C, the assembly 100 furthercomprises a manifold or connector 150 for joining the two or more of thecatheters 112, 114, 116 at a position outside the patient's body. Insome examples, the connector 150 can be a clamp, manifold, valve,fastener, or other element of a fluid path set, as is known in the art,for joining a catheter to external flexible tubing. As shown in FIGS.17A and 17B, the manifold or connector 150 comprises a two-piece bodycomprising an inner portion 151 mounted inside an outer housing 153. Theinner portion 151 defines channels for conducting fluid between inflowports 154, 155 and an outflow port 158. The inflow port(s) 154, 155 cancomprise threaded sockets 157 configured to receive proximal portions ofthe catheters 112, 114. Desirably, the sockets 157 are a suitable sizeto securely receive and hold flexible tubing sized between 1 Fr and 9Fr. Generally, a user cinches the sockets 157 around the respectivecatheter tubes 122 by spinning the socket 157 into the ports 154, 155 inthe direction of arrow A1 (shown in FIG. 17B).

Once the catheters 112, 114 are mounted to the connector 150, urineentering the connector 150 through the vacuum inflow ports 154, 155 isdirected through a fluid conduit in the direction of arrow A2 (shown inFIG. 17B) to the vacuum outflow port 158. The vacuum outflow port 158can be connected to the fluid collection container 712 and/or pumpassembly 710 (shown in FIG. 19) by, for example, flexible tubing 166defining a fluid flow path.

With specific reference to FIG. 17C, another exemplary connector 150 canbe configured to connect three or more catheters 112, 114, 116 tooutflow ports 158, 162. The connector 150 can comprise a structure orbody having a distal side 152 comprising two or more vacuum inflow ports154, 155 configured to be connected to proximal ends of the ureteralcatheters 112, 114, and a separate gravity drainage port 156 configuredto connect to the proximal end of the bladder catheter 116. The vacuumports 154, 155 and/or proximal ends of the ureteral catheters 112, 114can comprise a specific configuration to ensure that the ureteralcatheters 112, 114 are connected to the vacuum source and not to someother fluid collection assembly. Similarly, the gravity drainage port156 and/or proximal end of the bladder catheter 116 can comprise anotherconnector configuration to ensure that the bladder catheter 116 and notone of the ureteral catheters 112, 114 is permitted to drain by gravitydrainage. In other examples, the ports 154, 155, 156 and/or proximalends of the catheters 112, 114, 116 can include visual indicia to assistin correctly setting up the fluid collection system.

In some examples, urine received in the vacuum ports 154, 155 can bedirected through a Y-shaped conduit to a single vacuum outflow port 158located on a proximal side 160 of the connector 150. As inpreviously-described examples, the vacuum outflow port 158 can beconnected to the fluid collection container 712 and/or pump 710 bysuitable flexible tubing or other conduits for drawing urine from thebody and for inducing negative pressure in the ureters and/or kidneys.In some examples, the outflow port 156 and/or connector 150 can beconfigured to attach only to vacuum sources or pumps operating within apredetermined pressure range or power level to prevent exposing theureteral catheters 112, 114 to elevated levels or intensity of negativepressure. The proximal side 160 of the connector 150 can also comprise agravity outflow port 162 in fluid communication with the inflow port156. The gravity outflow port 162 can be configured to be connecteddirectly to the urine collection container 712 for urine collection bygravity drainage.

With continued reference to FIG. 17C, in some examples, in order tofacilitate system setup and implementation, the vacuum outflow port 158and the gravity outflow port 162 are disposed in close proximity so thata single socket 164, bracket, or connector can be coupled to theconnector 150 to establish fluid communication with each port 158, 162.The single socket or connector can be coupled to a multi-conduit hose ortube (e.g., flexible tubing 166) having a first conduit in fluidcommunication with the pump 710 and a second conduit in fluidcommunication with the collection container 712. Accordingly, a user caneasily set up the external fluid collection system by inserting thesingle socket 164 in the connector 150 and connecting the respectiveconduits to one of the fluid collection container 712 and pump 710(shown in FIG. 19). In other examples, a length of flexible tubing 166is connected between the urine collection container 712 and the gravityoutflow port 162, and a separate length of flexible tubing is connectedbetween the pump 710 and the vacuum outflow port 158.

Exemplary Fluid Sensors:

With reference again to FIG. 1, in some examples, the assembly 100further comprises sensors 174 for monitoring fluid characteristics ofurine being collected from the ureters 6, 8 and/or bladder 10. Asdiscussed herein in connection with FIG. 19, information obtained fromthe sensors 174 can be transmitted to a central data collection moduleor processor and used, for example, to control operation of an externaldevice, such as the pump 710 (shown in FIG. 19). The sensors 174 can beintegrally formed with one or more of the catheters 112, 114, 116 suchas, for example, embedded in a wall of the catheter body or tube and influid communication with drainage lumens 124, 140. In other examples,one or more of the sensors 174 can be positioned in a fluid collectioncontainer 712 (shown in FIG. 19) or in internal circuitry of an externaldevice, such as the pump 710.

Exemplary sensors 174 that can be used with the urine collectionassembly 100 can comprise one or more of the following sensor types. Forexample, the catheter assembly 100 can comprise a conductance sensor orelectrode that samples conductivity of urine. The normal conductance ofhuman urine is about 5-10 mS/m. Urine having a conductance outside ofthe expected range can indicate that the patient is experiencing aphysiological problem, which requires further treatment or analysis. Thecatheter assembly 100 can also comprise a flow meter for measuring aflow rate of urine through the catheter(s) 112, 114, 116. Flow rate canbe used to determine a total volume of fluid excreted from the body. Thecatheter(s) 112, 114, 116 can also comprise a thermometer for measuringurine temperature. Urine temperature can be used to collaborate theconductance sensor. Urine temperature can also be used for monitoringpurposes, as urine temperature outside of a physiologically normal rangecan be indicative of certain physiological conditions. In some examples,the sensors 174 can be urine analyte sensors configured to measure aconcentration of creatinine and/or proteins in urine. For example,various conductivity sensors and optical spectrometry sensors may beused for determining analyte concentration in urine. Sensors based oncolor change reagent test strips may also be used for this purpose.

Method of Insertion of a Urine Collection Assembly:

Having described the urine collection assembly 100 including theureteral catheter retention portions and bladder anchor device (e.g., astandard or modified Foley-type catheter), methods for insertion anddeployment of the assemblies will now be discussed in detail.

With reference to FIG. 18A, steps for positioning a fluid collectionassembly in a patient's body and, optionally, for inducing negativepressure in a patient's ureter and/or kidneys are illustrated. As shownat box 610, a medical professional or caregiver inserts a flexible orrigid cystoscope through the patient's urethra and into the bladder toobtain visualization of the ureteral orifices or openings. Once suitablevisualization is obtained, as shown at box 612, a guidewire is advancedthrough the urethra, bladder, ureteral opening, ureter, and to a desiredfluid collection position, such as the renal pelvis of the kidney. Oncethe guidewire is advanced to the desired fluid collection position, aureteral catheter of the present invention (examples of which arediscussed in detail above) is inserted over the guidewire to the fluidcollection position, as shown at box 614. In some examples, the locationof the ureteral catheter can be confirmed by fluoroscopy, as shown atbox 616. Once the position of the distal end of the catheter isconfirmed, as shown at box 618, the retention portion of the ureteralcatheter can be deployed. For example, the guidewire can be removed fromthe catheter, thereby allowing the distal end and/or retention portionto transition to a deployed position. In some examples, the deployeddistal end portion of the catheter does not entirely occlude the ureterand/or renal pelvis, such that urine is permitted to pass outside thecatheter and through the ureters into the bladder. Since moving thecatheter can exert forces against urinary tract tissues, avoidingcomplete blockage of the ureters avoids application of force to theureter sidewalls, which may cause injury.

After the ureteral catheter is in place and deployed, the same guidewirecan be used to position a second ureteral catheter in the other ureterand/or kidney using the same insertion and positioning methods describedherein. For example, the cystoscope can be used to obtain visualizationof the other ureteral opening in the bladder, and the guidewire can beadvanced through the visualized ureteral opening to a fluid collectionposition in the other ureter. A catheter can be drawn alongside theguidewire and deployed in the manner described herein. Alternatively,the cystoscope and guidewire can be removed from the body. Thecystoscope can be reinserted into the bladder over the first ureteralcatheter. The cystoscope is used, in the manner described above, toobtain visualization of the ureteral opening and to assist in advancinga second guidewire to the second ureter and/or kidney for positioning ofthe second ureteral catheter. Once the ureteral catheters are in place,in some examples, the guidewire and cystoscope are removed. In otherexamples, the cystoscope and/or guidewire can remain in the bladder toassist with placement of the bladder catheter.

Optionally, a bladder catheter can also be used. Once the ureteralcatheters are in place, as shown at box 620, the medical professional orcaregiver can insert a distal end of a bladder catheter in a collapsedor contracted state through the urethra of the patient and into thebladder. The bladder catheter can be a conventional Foley bladdercatheter or a bladder catheter of the present invention as discussed indetail above. Once inserted in the bladder, as shown at box 622, ananchor connected to and/or associated with the bladder catheter isexpanded to a deployed position. For example, when an expandable orinflatable catheter is used, fluid may be directed through an inflationlumen of the bladder catheter to expand a balloon structure located inthe patient's bladder. In some examples, the bladder catheter isinserted through the urethra and into the bladder without using aguidewire and/or cystoscope. In other examples, the bladder catheter isinserted over the same guidewire used to position the ureteralcatheters. Accordingly, when inserted in this manner, the ureteralcatheters can be arranged to extend from the distal end of the bladdercatheter and, optionally, proximal ends of the ureteral catheters can bearranged to terminate in a drainage lumen of the bladder catheter.

In some examples, the urine is permitted to drain by gravity from theurethra. In other examples, a negative pressure is induced in theureteral catheter and/or bladder catheter to facilitate drainage of theurine.

With reference to FIG. 18B, steps for using the urine collectionassembly for inducement of negative pressure in the ureter(s) and/orkidney(s) are illustrated. As shown at box 624, after the indwellingportions of the bladder and/or ureteral catheters are correctlypositioned and anchoring/retention structures are deployed, the externalproximal ends of the catheter(s) are connected to fluid collection orpump assemblies. For example, the ureteral catheter(s) can be connectedto a pump for inducing negative pressure at the patient's renal pelvisand/or kidney. In a similar manner, the bladder catheter can beconnected directly to a urine collection container for gravity drainageof urine from the bladder or connected to a pump for inducing negativepressure at the bladder.

Once the catheter(s) and pump assembly are connected, negative pressureis applied to the renal pelvis and/or kidney and/or bladder through thedrainage lumens of the ureteral catheters and/or bladder catheter, asshown at box 626. The negative pressure is intended to countercongestion mediated interstitial hydrostatic pressures due to elevatedintra-abdominal pressure and consequential or elevated renal venouspressure or renal lymphatic pressure. The applied negative pressure istherefore capable of increasing flow of filtrate through the medullarytubules and of decreasing water and sodium re-absorption.

In some examples, mechanical stimulation can be provided to portions ofthe ureters and/or renal pelvis to supplement or modify therapeuticaffects obtained by application of negative pressure. For example,mechanical stimulation devices, such as linear actuators and other knowndevices for providing, for example, vibration waves, disposed in distalportions of the ureteral catheter(s) can be actuated. While notintending to be bound by theory, it is believed that such stimulationeffects adjacent tissues by, for example, stimulating nerves and/oractuating peristaltic muscles associated with the ureter(s) and/or renalpelvis. Stimulation of nerves and activation of muscles may producechanges in pressure gradients or pressure levels in surrounding tissuesand organs which may contribute to or, in some cases, enhancetherapeutic benefits of negative pressure therapy. In some examples, themechanical stimulation can comprise pulsating stimulation. In otherexamples, low levels of mechanical stimulation can be providedcontinuously as negative pressure is being provided through the ureteralcatheter(s). In other examples, inflatable portions of the ureteralcatheter could be inflated and deflated in a pulsating manner tostimulate adjacent nerve and muscle tissue, in a similar manner toactuation of the mechanical stimulation devices described herein.

As a result of the applied negative pressure, as shown at box 628, urineis drawn into the catheter at the plurality of drainage ports at thedistal end thereof, through the drainage lumen of the catheter, and to afluid collection container for disposal. As the urine is being drawn tothe collection container, at box 630, sensors disposed in the fluidcollection system provide a number of measurements about the urine thatcan be used to assess the volume of urine collected, as well asinformation about the physical condition of the patient and compositionof the urine produced. In some examples, the information obtained by thesensors is processed, as shown at box 632, by a processor associatedwith the pump and/or with another patient monitoring device and, at box634, is displayed to the user via a visual display of an associatedfeedback device.

Exemplary Fluid Collection System:

Having described an exemplary urine collection assembly and method ofpositioning such an assembly in the patient's body, with reference toFIG. 19, a system 700 for inducing negative pressure to a patient'sureter(s) and/or kidney(s) will now be described. The system 700 cancomprise the ureteral catheter(s), bladder catheter or the urinecollection assembly 100 described hereinabove. As shown in FIG. 19,ureteral catheters 112, 114 and/or the bladder catheter 116 of theassembly 100 are connected to one or more fluid collection containers712 for collecting urine drawn from the renal pelvis and/or bladder. Insome examples, the bladder catheter 116 and the ureteral catheters 112,114 are connected to different fluid collection containers 712. Thefluid collection container 712 connected to the ureteral catheter(s)112, 114 can be in fluid communication with an external fluid pump 710for generating negative pressure in the ureter(s) and kidney(s) throughthe ureteral catheter(s) 112, 114. As discussed herein, such negativepressure can be provided for overcoming interstitial pressure andforming urine in the kidney or nephron. In some examples, a connectionbetween the fluid collection container 712 and pump 710 can comprise afluid lock or fluid barrier to prevent air from entering the renalpelvis or kidney in case of incidental therapeutic or non-therapeuticpressure changes. For example, inflow and outflow ports of the fluidcontainer can be positioned below a fluid level in the container.Accordingly, air is prevented from entering medical tubing or thecatheter through either the inflow or outflow ports of the fluidcontainer 712. As discussed previously, external portions of the tubingextending between the fluid collection container 712 and the pump 710can include one or more filters to prevent urine and/or particulatesfrom entering the pump 710.

As shown in FIG. 19, the system 700 further comprises a controller 714,such as a microprocessor, electronically coupled to the pump 710 andhaving or associated with computer readable memory 716. In someexamples, the memory 716 comprises instructions that, when executed,cause the controller 714 to receive information from sensors 174 locatedon or associated with portions of the assembly 100. Information about acondition of the patient can be determined based on information from thesensors 174. Information from the sensors 174 can also be used todetermine and implement operating parameters for the pump 710.

In some examples, the controller 714 is incorporated in a separate andremote electronic device in communication with the pump 710, such as adedicated electronic device, computer, tablet PC, or smart phone.Alternatively, the controller 714 can be included in the pump 710 and,for example, can control both a user interface for manually operatingthe pump 710, as well as system functions such as receiving andprocessing information from the sensors 174.

The controller 714 is configured to receive information from the one ormore sensors 174 and to store the information in the associatedcomputer-readable memory 716. For example, the controller 714 can beconfigured to receive information from the sensor 174 at a predeterminedrate, such as once every second, and to determine a conductance based onthe received information. In some examples, the algorithm forcalculating conductance can also include other sensor measurements, suchas urine temperature, to obtain a more robust determination ofconductance.

The controller 714 can also be configured to calculate patient physicalstatistics or diagnostic indicators that illustrate changes in thepatient's condition over time. For example, the system 700 can beconfigured to identify an amount of total sodium excreted. The totalsodium excreted may be based, for example, on a combination of flow rateand conductance over a period of time.

With continued reference to FIG. 19, the system 700 can further comprisea feedback device 720, such as a visual display or audio system, forproviding information to the user. In some examples, the feedback device720 can be integrally formed with the pump 710.

Alternatively, the feedback device 720 can be a separate dedicated or amultipurpose electronic device, such as a computer, laptop computer,tablet PC, smart phone, or other handheld electronic devices. Thefeedback device 720 is configured to receive the calculated ordetermined measurements from the controller 714 and to present thereceived information to a user via the feedback device 720. For example,the feedback device 720 may be configured to display current negativepressure (in mmHg) being applied to the urinary tract. In otherexamples, the feedback device 720 is configured to display current flowrate of urine, temperature, current conductance in mS/m of urine, totalurine produced during the session, total sodium excreted during thesession, other physical parameters, or any combination thereof.

In some examples, the feedback device 720 further comprises a userinterface module or component that allows the user to control operationof the pump 710. For example, the user can engage or turn off the pump710 via the user interface. The user can also adjust pressure applied bythe pump 710 to achieve a greater magnitude or rate of sodium excretionand fluid removal.

Optionally, the feedback device 720 and/or pump 710 further comprise adata transmitter 722 for sending information from the device 720 and/orpump 710 to other electronic devices or computer networks. The datatransmitter 722 can utilize a short-range or long-range datacommunications protocol. An example of a short-range data transmissionprotocol is Bluetooth®. Long-range data transmission networks include,for example, Wi-Fi or cellular networks. The data transmitter 722 cansend information to a patient's physician or caregiver to inform thephysician or caregiver about the patient's current condition.Alternatively, or in addition, information can be sent from the datatransmitter 722 to existing databases or information storage locations,such as, for example, to include the recorded information in a patient'selectronic health record (EHR).

With continued reference to FIG. 19, in addition to the urine sensors174, in some examples, the system 700 further comprises one or morepatient monitoring sensors 724. Patient monitoring sensors 724 caninclude invasive and non-invasive sensors for measuring informationabout the patient's urine composition, as discussed in detail above,blood composition (e.g., hematocrit ratio, analyte concentration,protein concentration, creatinine concentration) and/or blood flow(e.g., blood pressure, blood flow velocity). Hematocrit is a ratio ofthe volume of red blood cells to the total volume of blood. Normalhematocrit is about 25% to 40%, and preferably about 35% and 40% (e.g.,35% to 40% red blood cells by volume and 60% to 65% plasma).

Non-invasive patient monitoring sensors 724 can include pulse oximetrysensors, blood pressure sensors, heart rate sensors, and respirationsensors (e.g., a capnography sensor). Invasive patient monitoringsensors 724 can include invasive blood pressure sensors, glucosesensors, blood velocity sensors, hemoglobin sensors, hematocrit sensors,protein sensors, creatinine sensors, and others. In still otherexamples, sensors may be associated with an extracorporeal blood systemor circuit and configured to measure parameters of blood passing throughtubing of the extracorporeal system. For example, analyte sensors, suchas capacitance sensors or optical spectroscopy sensors, may beassociated with tubing of the extracorporeal blood system to measureparameter values of the patient's blood as it passes through the tubing.The patient monitoring sensors 724 can be in wired or wirelesscommunication with the pump 710 and/or controller 714.

In some examples, the controller 714 is configured to cause the pump 710to provide treatment for a patient based information obtained from theurine analyte sensor 174 and/or patient monitoring sensors 724, such asblood monitoring sensors. For example, pump 710 operating parameters canbe adjusted based on changes in the patient's blood hematocrit ratio,blood protein concertation, creatinine concentration, urine outputvolume, urine protein concentration (e.g., albumin), and otherparameters. For example, the controller 714 can be configured to receiveinformation about a blood hematocrit ratio or creatinine concentrationof the patient from the patient monitoring sensors 724 and/or analytesensors 174. The controller 714 can be configured to adjust operatingparameters of the pump 710 based on the blood and/or urine measurements.In other examples, hematocrit ratio may be measured from blood samplesperiodically obtained from the patient. Results of the tests can bemanually or automatically provided to the controller 714 for processingand analysis.

As discussed herein, measured hematocrit values for the patient can becompared to predetermined threshold or clinically acceptable values forthe general population. Generally, hematocrit levels for females arelower than for males. In other examples, measured hematocrit values canbe compared to patient baseline values obtained prior to a surgicalprocedure. When the measured hematocrit value is increased to within theacceptable range, the pump 710 may be turned off ceasing application ofnegative pressure to the ureter or kidneys. In a similar manner, theintensity of negative pressure can be adjusted based on measuredparameter values. For example, as the patient's measured parametersbegin to approach the acceptable range, intensity of negative pressurebeing applied to the ureter and kidneys can be reduced. In contrast, ifan undesirable trend (e.g., a decrease in hematocrit value, urine outputrate, and/or creatinine clearance) is identified, the intensity ofnegative pressure can be increased in order to produce a positivephysiological result. For example, the pump 710 may be configured tobegin by providing a low level of negative pressure (e.g., between about0.1 mmHg and 10 mmHg). The negative pressure may be incrementallyincreased until a positive trend in patient creatinine level isobserved. However, generally, negative pressure provided by the pump 710will not exceed about 50 mmHg.

With reference to FIGS. 20A and 20B, an exemplary pump 710 for use withthe system is illustrated. In some examples, the pump 710 is amicro-pump configured to draw fluid from the catheter(s) 112, 114(shown, for example, in FIG. 1) and having a sensitivity or accuracy ofabout 10 mmHg or less. Desirably, the pump 710 is capable of providing arange of flow of urine between 0.05 ml/min and 3 ml/min for extendedperiods of time, for example, for about 8 hours to about 24 hours perday, for one (1) to about 30 days or longer. At 0.2 ml/min, it isanticipated that about 300 mL of urine per day is collected by thesystem 700. The pump 710 can be configured to provide a negativepressure to the bladder of the patient, the negative pressure rangingbetween about 0.1 mmHg and 50 mmHg or about 5 mmHg to about 20 mmHg(gauge pressure at the pump 710). For example, a micro-pump manufacturedby Langer Inc. (Model BT100-2J) can be used with the presently disclosedsystem 700. Diaphragm aspirator pumps, as well as other types ofcommercially available pumps, can also be used for this purpose.Peristaltic pumps can also be used with the system 700. In otherexamples, a piston pump, vacuum bottle, or manual vacuum source can beused for providing negative pressure. In other examples, the system canbe connected to a wall suction source, as is available in a hospital,through a vacuum regulator for reducing negative pressure totherapeutically appropriate levels.

In some examples, the pump 710 is configured for extended use and, thus,is capable of maintaining precise suction for extended periods of time,for example, for about 8 hours to about 24 hours per day, for 1 to about30 days or longer. Further, in some examples, the pump 710 is configuredto be manually operated and, in that case, includes a control panel 718that allows a user to set a desired suction value. The pump 710 can alsoinclude a controller or processor, which can be the same controller thatoperates the system 700 or can be a separate processor dedicated foroperation of the pump 710. In either case, the processor is configuredfor both receiving instructions for manual operation of the pump and forautomatically operating the pump 710 according to predeterminedoperating parameters. Alternatively, or in addition, operation of thepump 710 can be controlled by the processor based on feedback receivedfrom the plurality of sensors associated with the catheter.

In some examples, the processor is configured to cause the pump 710 tooperate intermittently. For example, the pump 710 may be configured toemit pulses of negative pressure followed by periods in which nonegative pressure is provided. In other examples, the pump 710 can beconfigured to alternate between providing negative pressure and positivepressure to produce an alternating flush and pump effect. For example, apositive pressure of about 0.1 mmHg to 20 mmHg, and preferably about 5mmHg to 20 mmHg can be provided followed by a negative pressure rangingfrom about 0.1 mmHg to 50 mmHg.

Treatment for Removing Excess Fluid from a Patient with Hemodilution

According to another aspect of the disclosure, a method for removingexcess fluid from a patient with hemodilution is provided. In someexamples, hemodilution can refer to an increase in a volume of plasma inrelation to red blood cells and/or a reduced concentration of red bloodcells in circulation, as may occur when a patient is provided with anexcessive amount of fluid. The method can involve measuring and/ormonitoring patient hematocrit levels to determine when hemodilution hasbeen adequately addressed. Low hematocrit levels are a commonpost-surgical or post-trauma condition that can lead to undesirabletherapeutic outcomes. As such, management of hemodilution and confirmingthat hematocrit levels return to normal ranges is a desirabletherapeutic result for surgical and post-surgical patient care.

Steps for removing excess fluid from a patient using the devices andsystems described herein are illustrated in FIG. 24. As shown in FIG.24, the treatment method comprises deploying a urinary tract catheter,such as a ureteral catheter, in the ureter and/or kidney of a patientsuch that flow of urine from the ureter and/or kidney, as shown at box910. The catheter may be placed to avoid occluding the ureter and/orkidney. In some examples, a fluid collecting portion of the catheter maybe positioned in the renal pelvis of the patient's kidney. In someexamples, a ureter catheter may be positioned in each of the patient'skidneys. In other examples, a urine collection catheter may be deployedin the bladder or ureter. In some examples, the ureteral cathetercomprises one or more of any of the retention portions described herein.For example, the ureteral catheter can comprise a tube defining adrainage lumen comprising a helical retention portion and a plurality ofdrainage ports. In other examples, the catheter can include aninflatable retention portion (e.g., a balloon catheter), funnel-shapedfluid collection and retention portion, or a pigtail coil.

As shown at box 912, the method further comprises applying negativepressure to the ureter and/or kidney through the catheter to induceproduction of urine in the kidney(s) and to extract urine from thepatient. Desirably, negative pressure is applied for a period of timesufficient to reduce the patient's blood creatinine levels by aclinically significant amount.

Negative pressure may continue to be applied for a predetermined periodof time. For example, a user may be instructed to operate the pump forthe duration of a surgical procedure or for a time period selected basedon physiological characteristics of the patient. In other examples,patient condition may be monitored to determine when sufficienttreatment has been provided. For example, as shown at box 914, themethod may further comprise monitoring the patient to determine when tocease applying negative pressure to the patient's ureter and/or kidneys.In a preferred and non-limiting example, a patient's hematocrit level ismeasured. For example, patient monitoring devices may be used toperiodically obtain hematocrit values. In other examples, blood samplesmay be drawn periodically to directly measure hematocrit. In someexamples, concentration and/or volume of urine expelled from the bodythrough the catheter may also be monitored to determine a rate at whichurine is being produced by the kidneys. In a similar manner, expelledurine output may be monitored to determine protein concentration and/orcreatinine clearance rate for the patient. Reduced creatinine andprotein concentration in urine may be indicative of over-dilution and/ordepressed renal function. Measured values can be compared to thepredetermined threshold values to assess whether negative pressuretherapy is improving patient condition, and should be modified ordiscontinued. For example, as discussed herein, a desirable range forpatient hematocrit may be between 25% and 40%. In other preferred andnon-limiting examples, as described herein, patient body weight may bemeasured and compared to a dry body weight. Changes in measured patientbody weight demonstrate that fluid is being removed from the body. Assuch, a return to dry body weight represents that hemodilution has beenappropriately managed and the patient is not over-diluted.

As shown at box 916, a user may cause the pump to cease providingnegative pressure therapy when a positive result is identified. In asimilar manner, patient blood parameters may be monitored to assesseffectiveness of the negative pressure being applied to the patient'skidneys. For example, a capacitance or analyte sensor may be placed influid communication with tubing of an extracorporeal blood managementsystem. The sensor may be used to measure information representative ofblood protein, oxygen, creatinine, and/or hematocrit levels. Measuredblood parameter values may be measured continuously or periodically andcompared to various threshold or clinically acceptable values. Negativepressure may continue to be applied to the patient's kidney or ureteruntil a measured parameter value falls within a clinically acceptablerange. Once a measured values fails within the threshold or clinicallyacceptable range, as shown at box 916, application of negative pressuremay cease.

Treatment of Patients Undergoing a Fluid Resuscitation Procedure

According to another aspect of the disclosure, a method for removingexcess fluid for a patient undergoing a fluid resuscitation procedure,such as coronary graft bypass surgery, by removing excess fluid from thepatient is provided. During fluid resuscitation, solutions such assaline solutions and/or starch solutions, are introduced to thepatient's bloodstream by a suitable fluid delivery process, such as anintravenous drip. For example, in some surgical procedures, a patientmay be supplied with between 5 and 10 times a normal daily intake offluid. Fluid replacement or fluid resuscitation can be provided toreplace bodily fluids lost through sweating, bleeding, dehydration, andsimilar processes. In the case of a surgical procedure such as coronarygraft bypass, fluid resuscitation is provided to help maintain apatient's fluid balance and blood pressure within an appropriate rate.Acute kidney injury (AKI) is a known complication of coronary arterygraft bypass surgery. AKI is associated with a prolonged hospital stayand increased morbidity and mortality, even for patients who do notprogress to renal failure. See Kim, et al., Relationship between aperioperative intravenous fluid administration strategy and acute kidneyinjury following off-pump coronary artery bypass surgery: anobservational study, Critical Care 19:350 (1995). Introducing fluid toblood also reduces hematocrit levels which has been shown to furtherincrease mortality and morbidity. Research has also demonstrated thatintroducing saline solution to a patient may depress renal functionaland/or inhibit natural fluid management processes. As such, appropriatemonitoring and control of renal function may produce improved outcomesand, in particular, may reduce post-operative instances of AKI.

A method of treating a patient undergoing fluid resuscitation isillustrated in FIG. 25. As shown at box 1010, the method comprisesdeploying a ureteral catheter in the ureter and/or kidney of a patientsuch that flow of urine from the ureter and/or kidney is not preventedby occlusion of the ureter and/or kidney. For example, a fluidcollecting portion of the catheter may be positioned in the renalpelvis. In other examples, the catheter may be deployed in the bladderor ureter. The catheter can comprise one or more of the ureter cathetersdescribed herein. For example, the catheter can comprise a tube defininga drainage lumen and comprising a helical retention portion and aplurality of drainage ports. In other examples, the catheter can includean inflatable retention portion (e.g., a balloon catheter) or a pigtailcoil.

As shown at box 1012, optionally, a bladder catheter may also bedeployed in the patient's bladder. For example, the bladder catheter maybe positioned to seal the urethra opening to prevent passage of urinefrom the body through the urethra. The bladder catheter can include aninflatable anchor (e.g., a Foley catheter) for maintaining the distalend of the catheter in the bladder. As described herein, otherarrangements of coils and helices may also be used to obtain properpositioning of the bladder catheter. The bladder catheter can beconfigured to collect urine which entered the patient's bladder prior toplacement of the ureteral catheter(s). The bladder catheter may alsocollect urine which flows past the fluid collection portion(s) of theureteral catheter and enters the bladder. In some examples, a proximalportion of the ureteral catheter may be positioned in a drainage lumenof the bladder catheter. In a similar manner, the bladder catheter maybe advanced into the bladder using the same guidewire used forpositioning of the ureteral catheter(s). In some examples, negativepressure may be provided to the bladder through the drainage lumen ofthe bladder catheter. In other examples, negative pressure may only beapplied to the ureteral catheter(s). In that case, the bladder catheterdrains by gravity.

As shown at box 1014, following deployment of the ureteral catheter(s),negative pressure is applied to the ureter and/or kidney through theureteral catheter(s). For example, negative pressure can be applied fora period of time sufficient to extract urine comprising a portion of thefluid provided to the patient during the fluid resuscitation procedure.As described herein, negative pressure can be provided by an externalpump connected to a proximal end or port of the catheter. The pump canbe operated continually or periodically dependent on therapeuticrequirements of the patient. In some cases, the pump may alternatebetween applying negative pressure and positive pressure.

Negative pressure may continue to be applied for a predetermined periodof time. For example, a user may be instructed to operate the pump forthe duration of a surgical procedure or for a time period selected basedon physiological characteristics of the patient. In other examples,patient condition may be monitored to determine when a sufficient amountof fluid has been drawn from the patient. For example, as shown at box1016, fluid expelled from the body may be collected and a total volumeof obtained fluid may be monitored. In that case, the pump can continueto operate until a predetermined fluid volume has been collected fromthe ureteral and/or bladder catheters. The predetermined fluid volumemay be based, for example, on a volume of fluid provided to the patientprior to and during the surgical procedure. As shown at box 1018,application of negative pressure to the ureter and/or kidneys is stoppedwhen the collected total volume of fluid exceeds the predetermined fluidvolume.

In other examples, operation of the pump can be determined based onmeasured physiological parameters of the patient, such as measuredcreatinine clearance, blood creatinine level, or hematocrit ratio. Forexample, as shown at box 1020, urine collected form the patient may beanalyzed by one or more sensors associated with the catheter and/orpump. The sensor can be a capacitance sensor, analyte sensor, opticalsensor, or similar device configured to measure urine analyteconcentration. In a similar manner, as shown at box 1022, a patient'sblood creatinine or hematocrit level could be analyzed based oninformation obtain from the patient monitoring sensors discussedhereinabove. For example, a capacitance sensor may be placed in anexisting extracorporeal blood system. Information obtained by thecapacitance sensor may be analyzed to determine a patient's hematocritratio. The measured hematocrit ratio may be compared to certain expectedor therapeutically acceptable values. The pump may continue to applynegative pressure to the patient's ureter and/or kidney until measuredvalues within the therapeutically acceptable range are obtained. Once atherapeutically acceptable value is obtained, application of negativepressure may be stopped as shown at box 1018.

In other examples, as shown at box 2024, patient body weight may bemeasured to assess whether fluid is being removed from the patient bythe applied negative pressure therapy. For example, a patient's measuredbodyweight (including fluid introduced during a fluid resuscitationprocedure) can be compared to a patient's dry body weight. As usedherein, dry weights is defined as normal body weight measured when apatient is not over-diluted. For example, a patient who is notexperiencing one or more of: elevated blood pressure, lightheadedness orcramping, swelling of legs, feet, arms, hands, or around the eyes, andwho is breathing comfortably, likely does not have excess fluid. Aweight measured when the patient is not experiencing such symptoms canbe a dry body weight. Patient weight can be measured periodically untilthe measured weight approaches the dry body weight. When the measuredweight approaches (e.g., is within between 5% and 10% of dry bodyweight), as shown at box 1018, application of negative pressure can bestopped.

EXPERIMENTAL EXAMPLES

Inducement of negative pressure within the renal pelvis of farm swinewas performed for the purpose of evaluating effects of negative pressuretherapy on renal congestion in the kidney. An objective of these studieswas to demonstrate whether a negative pressure delivered into the renalpelvis significantly increases urine output in a swine model of renalcongestion. In Example 1, a pediatric Fogarty catheter, normally used inembolectomy or bronchoscopy applications, was used in the swine modelsolely for proof of principle for inducement of negative pressure in therenal pelvis. It is not suggested that a Fogarty catheter be used inhumans in clinical settings to avoid injury of urinary tract tissues. InExample 2, the ureteral catheter 112 shown in FIGS. 2A and 2B, andincluding a helical retention portion for mounting or maintaining adistal portion of the catheter in the renal pelvis or kidney, was used.

Example 1

Method

Four farm swine 800 were used for purposes of evaluating effects ofnegative pressure therapy on renal congestion in the kidney. As shown inFIG. 21, pediatric Fogarty catheters 812, 814 were inserted to the renalpelvis region 820, 821 of each kidney 802, 804 of the four swine 800.The catheters 812, 814 were deployed within the renal pelvis region byinflating an expandable balloon to a size sufficient to seal the renalpelvis and to maintain the position of the balloon within the renalpelvis. The catheters 812, 814 extend from the renal pelvis 802, 804,through a bladder 810 and urethra 816, and to fluid collectioncontainers external to the swine.

Urine output of two animals was collected for a 15 minute period toestablish a baseline for urine output volume and rate. Urine output ofthe right kidney 802 and the left kidney 804 were measured individuallyand found to vary considerably. Creatinine clearance values were alsodetermined.

Renal congestion (e.g., congestion or reduced blood flow in the veins ofthe kidney) was induced in the right kidney 802 and the left kidney 804of the animal 800 by partially occluding the inferior vena cava (IVC)with an inflatable balloon catheter 850 just above to the renal veinoutflow. Pressure sensors were used to measure IVC pressure. Normal IVCpressures were 1-4 mmHg. By inflating the balloon of the catheter 850 toapproximately three quarters of the IVC diameter, the IVC pressures wereelevated to between 15-25 mmHg. Inflation of the balloon toapproximately three quarters of IVC diameter resulted in a 50-85%reduction in urine output. Full occlusion generated IVC pressures above28 mmHg and was associated with at least a 95% reduction in urineoutput.

One kidney of each animal 800 was not treated and served as a control(“the control kidney 802”). The ureteral catheter 812 extending from thecontrol kidney was connected to a fluid collection container 819 fordetermining fluid levels. One kidney (“the treated kidney 804”) of eachanimal was treated with negative pressure from a negative pressuresource (e.g., a therapy pump 818 in combination with a regulatordesigned to more accurately control the low magnitude of negativepressures) connected to the ureteral catheter 814. The pump 818 was anAir Cadet Vacuum Pump from Cole-Parmer Instrument Company (Model No.EW-07530-85). The pump 818 was connected in series to the regulator. Theregulator was a V-800 Series Miniature Precision Vacuum Regulator—⅛ NPTPorts (Model No. V-800-10-W/K), manufactured by Airtrol Components Inc.

The pump 818 was actuated to induce negative pressure within the renalpelvis 820, 821 of the treated kidney according to the followingprotocol. First, the effect of negative pressure was investigated in thenormal state (e.g., without inflating the IVC balloon). Four differentpressure levels (−2, −10, −15, and −20 mmHg) were applied for 15 minuteseach and the rate of urine produced and creatinine clearance weredetermined. Pressure levels were controlled and determined at theregulator. Following the −20 mmHg therapy, the IVC balloon was inflatedto increase the pressure by 15-20 mmHg. The same four negative pressurelevels were applied. Urine output rate and creatinine clearance rate forthe congested control kidney 802 and treated kidney 804 were obtained.The animals 800 were subject to congestion by partial occlusion of theIVC for 90 minutes. Treatment was provided for 60 minutes of the 90minute congestion period.

Following collection of urine output and creatinine clearance data,kidneys from one animal were subjected to gross examination then fixedin a 10% neutral buffered formalin. Following gross examination,histological sections were obtained, examined, and magnified images ofthe sections were captured. The sections were examined using an uprightOlympus BX41 light microscope and images were captured using an OlympusDP25 digital camera. Specifically, photomicrograph images of the sampledtissues were obtained at low magnification (20× original magnification)and high magnification (100× original magnification). The obtainedimages were subjected to histological evaluation. The purpose of theevaluation was to examine the tissue histologically and to qualitativelycharacterize congestion and tubular degeneration for the obtainedsamples.

Surface mapping analysis was also performed on obtained slides of thekidney tissue. Specifically, the samples were stained and analyzed toevaluate differences in size of tubules for treated and untreatedkidneys. Image processing techniques calculated a number and/or relativepercentage of pixels with different coloration in the stained images.Calculated measurement data was used to determine volumes of differentanatomical structures.

Results

Urine Output and Creatinine Clearance

Urine output rates were highly variable. Three sources of variation inurine output rate were observed during the study. The inter-individualand hemodynamic variability were anticipated sources of variabilityknown in the art. A third source of variation in urine output, uponinformation and belief believed to be previously unknown, was identifiedin the experiments discussed herein, namely, contralateralintra-individual variability in urine output.

Baseline urine output rates were 0.79 ml/min for one kidney and 1.07ml/min for the other kidney (e.g., a 26% difference). The urine outputrate is a mean rate calculated from urine output rates for each animal.

When congestion was provided by inflating the IVC balloon, the treatedkidney urine output dropped from 0.79 ml/min to 0.12 ml/min (15.2% ofbaseline). In comparison, the control kidney urine output rate duringcongestion dropped from 1.07 ml/min to 0.09 ml/min (8.4% of baseline).Based on urine output rates, a relative increase in treated kidney urineoutput compared to control kidney urine output was calculated, accordingto the following equation:

(Therapy Treated/Baseline Treated)/(Therapy Control/BaselineControl)=Relative increase

(0.12 ml/min/0.79 ml/min)/(0.09 ml/min/1.07 ml/min)=180.6%

Thus, the relative increase in treated kidney urine output rate was180.6% compared to control. This result shows a greater magnitude ofdecrease in urine production caused by congestion on the control sidewhen compared to the treatment side. Presenting results as a relativepercentage difference in urine output adjusts for differences in urineoutput between kidneys.

Creatinine clearance measurements for baseline, congested, and treatedportions for one of the animals are shown in FIG. 22.

Gross Examination and Histological Evaluation

Based on gross examination of the control kidney (right kidney) andtreated kidney (left kidney), it was determined that the control kidneyhad a uniformly dark red-brown color, which corresponds with morecongestion in the control kidney compared to the treated kidney.Qualitative evaluation of the magnified section images also notedincreased congestion in the control kidney compared to the treatedkidney. Specifically, as shown in Table 1, the treated kidney exhibitedlower levels of congestion and tubular degeneration compared to thecontrol kidney. The following qualitative scale was used for evaluationof the obtained slides.

Lesion Score Congestion None: 0 Mild: 1 Moderate: 2 Marked: 3 Severe: 4Tubular degeneration None: 0 Mild: 1 Moderate: 2 Marked: 3 Severe: 4

TABLE 1 TABULATED RESULTS Histologic lesions Animal ID/Organ/Grosslesion Slide number Congestion Tubular hyaline casts Granulomas6343/Left Kidney/ R16-513-1 1 1 0 Normal 6343/Left Kidney/ R16-513-2 1 10 Normal with hemorrhagic streak 6343/Right Kidney/ R16-513-3 2 2 1Congestion 6343/Right Kidney/ R16-513-4 2 1 1 Congestion

As shown in Table 1, the treated kidney (left kidney) exhibited onlymild congestion and tubular degeneration. In contrast, the controlkidney (right kidney) exhibited moderate congestion and tubulardegeneration. These results were obtained by analysis of the slidesdiscussed below.

FIGS. 23A and 23B are low and high magnification photomicrographs of theleft kidney (treated with negative pressure) of the animal. Based on thehistological review, mild congestion in the blood vessels at thecorticomedullary junction was identified, as indicated by the arrows. Asshown in FIG. 23B, a single tubule with a hyaline cast (as identified bythe asterisk) was identified.

FIGS. 23C and 23D are low and high resolution photomicrographs of thecontrol kidney (right kidney). Based on the histological review,moderate congestion in the blood vessel at the corticomedullary junctionwas identified, as shown by the arrows in FIG. 23C. As shown in FIG.23D, several tubules with hyaline casts were present in the tissuesample (as identified by asterisks in the image). Presence of asubstantial number of hyaline casts is evidence of hypoxia.

Surface mapping analysis provided the following results. The treatedkidney was determined to have 1.5 times greater fluid volume in Bowman'sspace and 2 times greater fluid volume in tubule lumen. Increased fluidvolume in Bowman's space and the tubule lumen corresponds to increasedurine output. In addition, the treated kidney was determined to have 5times less blood volume in capillaries compared to the control kidney.The increased volume in the treated kidney appears to be a result of (1)a decrease in individual capillary size compared to the control and (2)an increase in the number of capillaries without visible red blood cellsin the treated kidney compared to the control kidney, an indicator ofless congestion in the treated organ.

Summary

These results indicate that the control kidney had more congestion andmore tubules with intraluminal hyaline casts, which representprotein-rich intraluminal material, compared to the treated kidney.Accordingly, the treated kidney exhibits a lower degree of loss of renalfunction. While not intending to be bound by theory, it is believed thatas severe congestion develops in the kidney, hypoxemia of the organfollows. Hypoxemia interferes with oxidative phosphorylation within theorgan (e.g., ATP production). Loss of ATP and/or a decrease in ATPproduction inhibits the active transport of proteins causingintraluminal protein content to increase, which manifests as hyalinecasts. The number of renal tubules with intraluminal hyaline castscorrelates with the degree of loss of renal function. Accordingly, thereduced number of tubules in the treated left kidney is believed to bephysiologically significant. While not intending to be bound by theory,it is believed that these results show that damage to the kidney can beprevented or inhibited by applying negative pressure to a catheterinserted into the renal pelvis to facilitate urine output.

Example 2

Method

Four (4) farm swine (A, B, C, D) were sedated and anesthetized. Vitalsfor each of the swine were monitored throughout the experiment andcardiac output was measured at the end of each 30-minute phase of thestudy. Ureteral catheters, such as the ureteral catheter 112 shown inFIGS. 2A and 2B, were deployed in the renal pelvis region of the kidneysof each of the swine. The deployed catheters were a 6 Fr catheter havingan outer diameter of 2.0±0.1 mm. The catheters were 54±2 cm in length,not including the distal retention portion. The retention portion was16±2 mm in length. As shown in the catheter 112 in FIGS. 2A and 2B, theretention portion included two full coils and one proximal half coil.The outer diameter of the full coils, shown by line D1 in FIGS. 2A and2B, was 18±2 mm. The half coil diameter D2 was about 14 mm. Theretention portion of the deployed ureteral catheters included sixdrainage holes, plus an additional hole at the distal end of thecatheter tube. The diameter of each of the drainage holes was 0.83±0.01mm. The distance between adjacent drainage holes 132, specifically thelinear distance between drainage holes when the coils were straightened,was 22.5±2.5 mm.

The ureteral catheters were positioned to extend from the renal pelvisof the swine, through the bladder, and urethra, and to fluid collectioncontainers external to each swine. Following placement of the ureteralcatheters, pressure sensors for measuring IVC pressure were placed inthe IVC at a position distal to the renal veins. An inflatable ballooncatheter, specifically a PTS® percutaneous balloon catheter (30 mmdiameter by 5 cm length), manufactured by NuMED Inc. of Hopkinton, N.Y.,was expanded in the IVC at a position proximal to the renal veins. Athermodilution catheter, specifically a Swan-Ganz thermodilutionpulmonary artery catheter manufactured by Edwards Lifesciences Corp. ofIrvine, Calif., was then placed in the pulmonary artery for the purposeof measuring cardiac output.

Initially, baseline urine output was measured for 30 minutes, and bloodand urine samples were collected for biochemical analysis. Following the30-minute baseline period, the balloon catheter was inflated to increaseIVC pressure from a baseline pressure of 1-4 mmHg to an elevatedcongested pressure of about 20 mmHg (+/−5 mmHg). A congestion baselinewas then collected for 30 minutes with corresponding blood and urineanalysis.

At the end of the congestion period, the elevated congested IVC pressurewas maintained and negative pressure diuresis treatment was provided forswine A and swine C. Specifically, the swine (A, C) were treated byapplying a negative pressure of −25 mmHg through the ureteral catheterswith a pump. As in previously-discussed examples, the pump was an AirCadet Vacuum Pump from Cole-Parmer Instrument Company (Model No.EW-07530-85). The pump was connected in series to a regulator. Theregulator was a V-800 Series Miniature Precision Vacuum Regulator—⅛ NPTPorts (Model No. V-800-10-W/K), manufactured by Airtrol Components Inc.The swine were observed for 120 minutes, as treatment was provided.Blood and urine collection were performed every 30 minutes, during thetreatment period. Two of the swine (B, D) were treated as congestedcontrols (e.g., negative pressure was not applied to the renal pelvisthrough the ureteral catheters), meaning that the two swine (B, D) didnot receive negative pressure diuresis therapy.

Following collection of urine output and creatinine clearance data forthe 120-minute treatment period, the animals were sacrificed and kidneysfrom each animal were subjected to gross examination. Following grossexamination, histological sections were obtained and examined, andmagnified images of the sections were captured.

Results

Measurements collected during the Baseline, Congestion, and Treatmentperiods are provided in Table 2. Specifically, urine output, serumcreatinine, and urinary creatinine measurements were obtained for eachtime period. These values allow for the calculation of a measuredcreatinine clearance as follows:

${{Creatinine}\mspace{14mu}{{Clearance}:{CrCl}}} = {{Urine}\mspace{14mu}{Output}\mspace{14mu}\left( {m{l/\min}} \right)*\frac{{Urinary}\mspace{14mu}{Creatinine}\mspace{14mu}\left( {m{g/d}l} \right)}{{Serum}\mspace{14mu}{Creatinine}\mspace{14mu}\left( {m{g/d}l} \right)}}$

In addition, Neutrophil gelatinase-associated lipocalin (NGAL) valueswere measured from serum samples obtained for each time period andKidney Injury Molecule 1 (KIM-1) values were measured from the urinesamples obtained for each time period. Qualitative histological findingsdetermined from review of the obtained histological sections are alsoincluded in Table 2.

TABLE 2 Animal A B C D Treatment assignment Treatment Control TreatmentControl Baseline: Urine output (ml/min) 3.01 2.63 0.47 0.98 Serumcreatinine (mg/dl) 0.8 0.9 3.2 1.0 Creatinine clearance (ml/min) 261 1725.4 46.8 Serum NGAL (ng/ml) 169 * 963 99 Urinary KIM-1 (ng/ml) 4.11 *3.59 1.16 Congestion: Urine output (ml/min) 0.06 (2%) 0.53 (20%) 0.12(25%) 0.24 (25%) Serum creatinine (mg/dl) 1.2 (150%) 1.1 (122%) 3.1(97%) 1.2 (120%) Creatinine clearance (ml/min) 1.0 (0.4%) 30.8 (18%) 1.6(21%) 16.2 (35%) Serum NGAL (ng/ml) 102 (60%) * 809 (84%) 126 (127%)Urinary KIM-1 (ng/ml) 24.3 (591%) * 2.2 (61%) 1.39 (120%) Treatment:Urine output (ml/min) 0.54 (17%) ** 0.47 (101%) 0.35 (36%) Serumcreatinine (mg/dl) 1.3 (163%) 3.1 (97%) 1.7 (170%) Creatinine clearance(ml/min) 30.6 (12%) 18.3 (341%) 13.6 (29%) Serum NGAL (ng/ml) 197 (117%)1104 (115%) 208 (209%) Urinary KIM-1 (ng/ml) 260 (6326%) 28.7 (799%) 233(20000%) Histological findings: Blood volume in capillary space 2.4% **0.9% 4.0% Hyaline casts Mild/Mod None Mod Degranulation Mild/Mod NoneMod Data are raw values (% baseline) *not measured **confounded byphenylephrine

Animal A: The animal weighed 50.6 kg and had a baseline urine outputrate of 3.01 ml/min, a baseline serum creatinine of 0.8 mg/dl, and ameasured CrCl of 261 ml/min. It is noted that these measurements, asidefrom serum creatinine, were uncharacteristically high relative to otheranimals studied. Congestion was associated with a 98% reduction in urineoutput rate (0.06 ml/min) and a >99% reduction in CrCl (1.0 ml/min).Treatment with negative pressure applied through the ureteral catheterswas associated with urine output and CrCl of 17% and 12%, respectively,of baseline values, and 9× and >10×, respectively, of congestion values.Levels of NGAL changed throughout the experiment, ranging from 68% ofbaseline during congestion to 258% of baseline after 90 minutes oftherapy. The final value was 130% of baseline. Levels of KIM-1 were 6times and 4 times of baseline for the first two 30-minute windows afterbaseline assessment, before increasing to 68×, 52×, and 63× of baselinevalues, respectively, for the last three collection periods. The 2-hourserum creatinine was 1.3 mg/dl. Histological examination revealed anoverall congestion level, measured by blood volume in capillary space,of 2.4%. Histological examination also noted several tubules withintraluminal hyaline casts and some degree of tubular epithelialdegeneration, a finding consistent with cellular damage.

Animal B: The animal weighed 50.2 kg and had a baseline urine outputrate of 2.62 ml/min and a measured CrCl of 172 ml/min (also higher thananticipated). Congestion was associated with an 80% reduction in urineoutput rate (0.5 ml/min) and an 83% reduction in CrCl (30 ml/min). At 50minutes into the congestion (20 minutes after the congestion baselineperiod), the animal experienced an abrupt drop in mean arterial pressureand respiration rate, followed by tachycardia. The anesthesiologistadministered a dose of phenylephrine (75 mg) to avert cardiogenic shock.Phenylephrine is indicated for intravenous administration when bloodpressure drops below safe levels during anesthesia. However, since theexperiment was testing the impact of congestion on renal physiology,administration of phenylephrine confounded the remainder of theexperiment.

Animal C: The animal weighed 39.8 kg and had a baseline urine outputrate of 0.47 ml/min, a baseline serum creatinine of 3.2 mg/dl, and ameasured CrCl of 5.4 ml/min. Congestion was associated with a 75%reduction in urine output (0.12 ml/min) and a 79% reduction in CrCl (1.6ml/min). It was determined that baseline NGAL levels were >5× the upperlimit of normal (ULN). Treatment with negative pressure applied to therenal pelvis through the ureteral catheters was associated with anormalization of urine output (101% of baseline) and a 341% improvementin CrCl (18.2 ml/min). Levels of NGAL changed throughout the experiment,ranging from 84% of baseline during congestion to 47% to 84% of baselinebetween 30 and 90 minutes. The final value was 115% of baseline. Levelsof KIM-1 decreased 40% from baseline within the first 30 minutes ofcongestion, before increasing to 8.7×, 6.7×, 6.6×, and 8× of baselinevalues, respectively, for the remaining 30-minute windows. Serumcreatinine level at 2 hours was 3.1 mg/dl. Histological examinationrevealed an overall congestion level, measured by blood volume incapillary space, of 0.9%. The tubules were noted to be histologicallynormal.

Animal D: The animal weighed 38.2 kg and had a baseline urine output of0.98 ml/min, a baseline serum creatinine of 1.0 mg/dl, and a measuredCrCl of 46.8 ml/min. Congestion was associated with a 75% reduction inurine output rate (0.24 ml/min) and a 65% reduction in Cr Cl (16.2ml/min). Continued congestion was associated with a 66% to 91% reductionof urine output and 89% to 71% reduction in CrCl. Levels of NGAL changedthroughout the experiment, ranging from 127% of baseline duringcongestion to a final value of 209% of baseline. Levels of KIM-1remained between 1× and 2× of baseline for the first two 30-minutewindows after baseline assessment, before increasing to 190×, 219×, and201× of baseline values for the last three 30-minute periods. The 2-hourserum creatinine level was 1.7 mg/dl. Histological examination revealedan overall congestion level 2.44× greater than that observed in tissuesamples for the treated animals (A, C) with an average capillary size2.33 times greater than that observed in either of the treated animals.The histological evaluation also noted several tubules with intraluminalhyaline casts as well as tubular epithelial degeneration, indicatingsubstantial cellular damage.

Summary

While not intending to be bound by theory, it is believed that thecollected data supports the hypothesis that venous congestion creates aphysiologically significant impact on renal function. In particular, itwas observed that elevation of the renal vein pressure reduced urineoutput by 75% to 98% within seconds. The association between elevationsin biomarkers of tubular injury and histological damage is consistentwith the degree of venous congestion generated, both in terms ofmagnitude and duration of the injury.

The data also appears to support the hypothesis that venous congestiondecreases the filtration gradients in the medullary nephrons by alteringthe interstitial pressures. The change appears to directly contribute tothe hypoxia and cellular injury within medullary nephrons. While thismodel does not mimic the clinical condition of AKI, it does provideinsight into the mechanical sustaining injury.

The data also appears to support the hypothesis that applying negativepressure to the renal pelvis through ureteral catheters can increaseurine output in a venous congestion model. In particular, negativepressure treatment was associated with increases in urine output andcreatinine clearance that would be clinically significant.Physiologically meaningful decreases in medullary capillary volume andsmaller elevations in biomarkers of tubular injury were also observed.Thus, it appears that by increasing urine output rate and decreasinginterstitial pressures in medullary nephrons, negative pressure therapymay directly decrease congestion. While not intending to be bound bytheory, by decreasing congestion, it may be concluded that negativepressure therapy reduces hypoxia and its downstream effects within thekidney in a venous congestion mediated AKI.

The experimental results appear to support the hypothesis that thedegree of congestion, both in terms of the magnitude of pressure andduration, is associated with the degree of cellular injury observed.Specifically, an association between the degree of urine outputreduction and the histological damage was observed. For example, treatedSwine A, which had a 98% reduction in urine output, experienced moredamage than treated Swine C, which had a 75% reduction in urine output.As would be expected, control Swine D, which was subjected to a 75%reduction in urine output without benefit of therapy for two and a halfhours, exhibited the most histological damage. These findings arebroadly consistent with human data demonstrating an increased risk forAKI onset with greater venous congestion. See e.g., Legrand, M. et al.,Association between systemic hemodynamics and septic acute kidney injuryin critically ill patients: a retrospective observational study.Critical Care 17:R278-86, 2013.

Example 3

Method

Inducement of negative pressure within the renal pelvis of farm swinewas performed for the purpose of evaluating effects of negative pressuretherapy on hemodilution of the blood. An objective of these studies wasto demonstrate whether a negative pressure delivered into the renalpelvis significantly increases urine output in a swine model of fluidresuscitation.

Two pigs were sedated and anesthetized using ketamine, midazolam,isoflurane and propofol. One animal (#6543) was treated with a ureteralcatheter and negative pressure therapy as described herein. The other,which received a Foley type bladder catheter, served as a control(#6566). Following placement of the catheters, the animals weretransferred to a sling and monitored for 24 hours.

Fluid overload was induced in both animals with a constant infusion ofsaline (125 mL/hour) during the 24 hour follow-up. Urine output volumewas measured at 15 minute increments for 24 hours. Blood and urinesamples were collected at 4 hour increments. As shown in FIG. 21, atherapy pump 818 was set to induce negative pressure within the renalpelvis 820, 821 (shown in FIG. 21) of both kidneys using a pressure of−45 mmHg (+/−2 mmHg).

Results

Both animals received 7 L of saline over the 24 hour period. The treatedanimal produced 4.22 L of urine while the control produced 2.11 L. Atthe end of 24 hours, the control had retained 4.94 L of the 7 Ladministered, while the treated animal retained 2.81 L of the 7 Ladministered. FIG. 26 illustrates the change in serum albumin. Thetreated animal had a 6% drop in the serum albumin concentration over 24hours, while the control animal had a 29% drop.

Summary

While not intending to be bound by theory, it is believed that thecollected data supports the hypothesis that fluid overload inducesclinically significant impact on renal function and, consequentlyinduces hemodilution. In particular, it was observed that administrationof large quantities of intravenous saline cannot be effectively removedby even healthy kidneys. The resulting fluid accumulation leads tohemodilution. The data also appears to support the hypothesis thatapplying negative pressure diuresis therapy to fluid overloaded animalscan increase urine output, improve net fluid balance and decrease theimpact of fluid resuscitation on development of hemodilution.

The preceding examples and embodiments of the invention have beendescribed with reference to various examples. Modifications andalterations will occur to others upon reading and understanding theforegoing examples. Accordingly, the foregoing examples are not to beconstrued as limiting the disclosure.

What is claimed is:
 1. A ureteral catheter, comprising: a drainage lumencomprising a proximal portion configured to be positioned in at least aportion of a patient's urethra and/or bladder and a distal portionconfigured to be positioned in a patient's kidney, renal pelvis, and/orin the ureter adjacent to the renal pelvis, the distal portioncomprising a retention portion for maintaining positioning of the distalportion of the drainage lumen, the retention portion comprising two ormore openings on a sidewall of the retention portion for permittingfluid flow into the drainage lumen, wherein a number of the openingsnearer to a distal end of the retention portion is greater than a numberof the opening(s) nearer to a proximal end of the retention portion. 2.The ureteral catheter of claim 1, wherein the proximal portion of thedrainage lumen is essentially free of or free of openings.
 3. Theureteral catheter of claim 1, wherein the proximal portion of thedrainage lumen is configured to extend outside of the patient's body. 4.The ureteral catheter of claim 1, wherein the retention portion furthercomprises: at least one first coil having a first diameter; and at leastone second coil having a second diameter, the first diameter being lessthan the second diameter, the second coil being closer to the distal endof the drainage lumen than the first coil.
 5. The ureteral catheter ofclaim 1, wherein the sidewall comprises a radially inwardly facing sideand a radially outwardly facing side, and wherein a total area of theopenings on the radially inwardly facing side is greater than a totalarea of the openings on the radially outwardly facing side.
 6. Theureteral catheter of claim 1, wherein the sidewall comprises a radiallyinwardly facing side and a radially outwardly facing side, and whereinone or more openings are disposed on the radially inwardly facing side,and wherein the radially outwardly facing side is essentially free orfree of openings.
 7. The ureteral catheter of claim 4, wherein theretention portion further comprises a third coil, the third coil havinga diameter greater than or equal to either the first diameter or thesecond diameter, the third coil being closer to an end of the distalportion of the drainage lumen than the second coil.
 8. The ureteralcatheter of claim 1, wherein a total area of the one or more openingsincreases for openings closer to a distal end of the retention portion.9. The ureteral catheter of claim 1, wherein the drainage lumencomprises an open distal end.
 10. The ureteral catheter of claim 1,wherein an area of a single opening closer to the proximal portion ofthe drainage lumen is less than an area of a single opening closer tothe distal end of the drainage lumen.
 11. The ureteral catheter of claim1, wherein an area of each single opening nearer to the proximal end ofthe retention portion is less than an area of a distally adjacent singleopening.
 12. The ureteral catheter of claim 1, wherein each of theopenings has the same area.
 13. The ureteral catheter of claim 1,wherein each opening is independently selected from one or more ofcircles, triangles, rectangles, ellipses, ovals, and squares.
 14. Theureteral catheter of claim 1, wherein less than 70%, or less than 55%,by volume of fluid flow is drawn into the drainage lumen through asingle opening positioned near the proximal end of the retentionportion.
 15. A system for inducing negative pressure in a portion of aurinary tract of a patient, the system comprising: at least one ureteralcatheter of claim 1; and a pressure source in fluid communication withthe drainage lumen of the at least one ureteral catheter, the pressuresource being configured for inducing a positive and/or a negativepressure in a portion of the urinary tract of the patient to draw fluidinto the drainage lumen through the openings of the retention portion.16. The system of claim 15, wherein the pressure source comprises apump.
 17. The system of claim 15, wherein the pump is configured tooperate at one of three pressure levels selected by a user, the pressurelevels generating a negative pressure of 15 mmHg, 30 mmHg, or 45 mmHg.18. The system of claim 15, wherein the pump is configured to alternatebetween generating negative pressure and generating positive pressure.19. The system of claim 15, further comprising: one or more sensors influid communication with the drainage lumen, the one or more sensorsbeing configured to determine information comprising at least one ofcapacitance, analyte concentration, and temperature of urine within thedrainage lumen; and a controller comprising computer readable memoryincluding programming instructions that, when executed, cause thecontroller to: receive the information from the one or more sensors andadjust an operating parameter of the pressure source based, at least inpart, on the information received from the one or more sensors toincrease or decrease vacuum pressure in the drainage lumen of the atleast one ureteral catheter to adjust flow of urine through the drainagelumen.
 20. The system of claim 15, comprising a first ureteral catheterconfigured to be placed in a first kidney, renal pelvis, and/or in theureter adjacent to the renal pelvis of the patient and a second ureteralcatheter configured to be placed in a second kidney, renal pelvis,and/or in the ureter adjacent to the renal pelvis of the patient,wherein the pressure source is configured to apply negative pressureindependently to the first ureteral catheter and the second ureteralcatheter such that the pressure in each catheter can be the same ordifferent from the other catheter.